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Erschienen in:

01.01.2007

Novel Analysis of Clonal Diversification in Blood B Cell and Bone Marrow Plasma Cell Clones in Immunoglobulin Light Chain Amyloidosis

verfasst von: ROSHINI S. ABRAHAM, MICHELLE K. MANSKE, NETA S. ZUCKERMAN, ABHISHEK SOHNI, HANNA EDELMAN, GITIT SHAHAF, MICHAEL M. TIMM, ANGELA DISPENZIERI, MORIE A. GERTZ, RAMIT MEHR

Erschienen in: Journal of Clinical Immunology | Ausgabe 1/2007

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Abstract

Immunoglobulin light chain amyloidosis (AL) is characterized by a limited clonal expansion of plasma cells and amyloid formation. Here, we report restriction in the diversity of VL gene usage with a dominance of clonally related B cells in the peripheral blood (PB) isotype-specific repertoire of AL patients. A rigorous quantification of lineage trees reveals presence of intraclonal variations in the PB clones compared to the bone marrow (BM) clones, which suggests a common precursor that is still subject to somatic mutation. When compared to normal BM and PB B cells, AL clones showed significant but incomplete impairment of antigenic selection, which could not be detected by conventional R and S mutation analysis. Therefore, graphical analysis of B cell lineage trees and mathematical quantification of tree properties provide novel insights into the process of B cell clonal evolution in AL.
Literatur
1.
Zurück zum Zitat Gertz MA, Kyle RA: Primary systemic amyloidosis—A diagnostic primer. Mayo Clinic Proc 64:1505–1519, 1989 Gertz MA, Kyle RA: Primary systemic amyloidosis—A diagnostic primer. Mayo Clinic Proc 64:1505–1519, 1989
2.
Zurück zum Zitat Gertz MA, Lacy MQ, Dispenzieri A: Amyloidosis. Hematol Oncol Clin North Am 13:1211–1233, 1999PubMedCrossRef Gertz MA, Lacy MQ, Dispenzieri A: Amyloidosis. Hematol Oncol Clin North Am 13:1211–1233, 1999PubMedCrossRef
3.
Zurück zum Zitat Kyle RA, Greipp PR: Amyloidosis (AL). Clinical and laboratory features in 229 cases. Mayo Clinic Proc 58:665–683, 1983 Kyle RA, Greipp PR: Amyloidosis (AL). Clinical and laboratory features in 229 cases. Mayo Clinic Proc 58:665–683, 1983
4.
Zurück zum Zitat Kyle RA, Gertz MA: Primary systemic amyloidosis: Clinical and laboratory features in 474 cases. Seminars Hematol 32:45–59, 1995 Kyle RA, Gertz MA: Primary systemic amyloidosis: Clinical and laboratory features in 474 cases. Seminars Hematol 32:45–59, 1995
5.
Zurück zum Zitat Billadeau D, Quam L, Thomas W, Kay N, Greipp P, Kyle R, Oken MM, Van Ness B: Detection and quantitation of malignant cells in the peripheral blood of multiple myeloma patients. Blood 80:1818–1824, 1992PubMed Billadeau D, Quam L, Thomas W, Kay N, Greipp P, Kyle R, Oken MM, Van Ness B: Detection and quantitation of malignant cells in the peripheral blood of multiple myeloma patients. Blood 80:1818–1824, 1992PubMed
6.
Zurück zum Zitat Billadeau D, Van Ness B, Kimlinger T, Kyle RA, Therneau TM, Greipp PR, Witzig TE: Clonal circulating cells are common in plasma cell proliferative disorders: A comparison of monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, and active myeloma. Blood 88:289–296, 1996PubMed Billadeau D, Van Ness B, Kimlinger T, Kyle RA, Therneau TM, Greipp PR, Witzig TE: Clonal circulating cells are common in plasma cell proliferative disorders: A comparison of monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, and active myeloma. Blood 88:289–296, 1996PubMed
7.
Zurück zum Zitat Rawstron AC, Owen RG, Davies FE, Johnson RJ, Jones RA, Richards SJ, Evans PA, Child JA, Smith GM, Jack AS, Morgan GJ: Circulating plasma cells in multiple myeloma: Characterization and correlation with disease stage.[see comment]. Br J Haematol 97:46–55, 1997PubMedCrossRef Rawstron AC, Owen RG, Davies FE, Johnson RJ, Jones RA, Richards SJ, Evans PA, Child JA, Smith GM, Jack AS, Morgan GJ: Circulating plasma cells in multiple myeloma: Characterization and correlation with disease stage.[see comment]. Br J Haematol 97:46–55, 1997PubMedCrossRef
8.
Zurück zum Zitat Witzig TE, Dhodapkar MV, Kyle RA, Greipp PR: Quantitation of circulating peripheral blood plasma cells and their relationship to disease activity in patients with multiple myeloma. Cancer 72:108–113, 1993PubMedCrossRef Witzig TE, Dhodapkar MV, Kyle RA, Greipp PR: Quantitation of circulating peripheral blood plasma cells and their relationship to disease activity in patients with multiple myeloma. Cancer 72:108–113, 1993PubMedCrossRef
9.
Zurück zum Zitat Witzig TE: Detection of malignant cells in the peripheral blood of patients with multiple myeloma: Clinical implications and research applications. Mayo Clin Proc 69:903–907, 1994PubMed Witzig TE: Detection of malignant cells in the peripheral blood of patients with multiple myeloma: Clinical implications and research applications. Mayo Clin Proc 69:903–907, 1994PubMed
10.
Zurück zum Zitat Witzig TE, Gertz MA, Pineda AA, Kyle RA, Greipp PR: Detection of monoclonal plasma cells in the peripheral blood stem cell harvests of patients with multiple myeloma. Br J Haematol 89:640–642, 1995PubMed Witzig TE, Gertz MA, Pineda AA, Kyle RA, Greipp PR: Detection of monoclonal plasma cells in the peripheral blood stem cell harvests of patients with multiple myeloma. Br J Haematol 89:640–642, 1995PubMed
11.
Zurück zum Zitat Witzig TE, Kimlinger TK, Ahmann GJ, Katzmann JA, Greipp PR: Detection of myeloma cells in the peripheral blood by flow cytometry. Cytometry 26:113–120, 1996PubMedCrossRef Witzig TE, Kimlinger TK, Ahmann GJ, Katzmann JA, Greipp PR: Detection of myeloma cells in the peripheral blood by flow cytometry. Cytometry 26:113–120, 1996PubMedCrossRef
12.
Zurück zum Zitat Witzig TE, Gertz MA, Lust JA, Kyle RA, Greipp PR: Serial studies of peripheral blood myeloma cells in patients with multiple myeloma: When is the optimal time for stem cell harvest? Leukemia Lymphoma 19:417–422, 1995PubMed Witzig TE, Gertz MA, Lust JA, Kyle RA, Greipp PR: Serial studies of peripheral blood myeloma cells in patients with multiple myeloma: When is the optimal time for stem cell harvest? Leukemia Lymphoma 19:417–422, 1995PubMed
13.
Zurück zum Zitat Rawstron AC, Davies FE, DasGupta R, Ashcroft AJ, Patmore R, Drayson MT, Owen RG, Jack AS, Child JA, Morgan GJ: Flow cytometric disease monitoring in multiple myeloma: The relationship between normal and neoplastic plasma cells predicts outcome after transplantation. Blood 100:3095–3100, 2002PubMedCrossRef Rawstron AC, Davies FE, DasGupta R, Ashcroft AJ, Patmore R, Drayson MT, Owen RG, Jack AS, Child JA, Morgan GJ: Flow cytometric disease monitoring in multiple myeloma: The relationship between normal and neoplastic plasma cells predicts outcome after transplantation. Blood 100:3095–3100, 2002PubMedCrossRef
14.
Zurück zum Zitat Gertz MA, Witzig TE, Pineda AA, Greipp PR, Kyle RA, Litzow MR: Monoclonal plasma cells in the blood stem cell harvest from patients with multiple myeloma are associated with shortened relapse-free survival after transplantation. Bone Marrow Transplant 19:337–342, 1997PubMedCrossRef Gertz MA, Witzig TE, Pineda AA, Greipp PR, Kyle RA, Litzow MR: Monoclonal plasma cells in the blood stem cell harvest from patients with multiple myeloma are associated with shortened relapse-free survival after transplantation. Bone Marrow Transplant 19:337–342, 1997PubMedCrossRef
15.
Zurück zum Zitat Comenzo RL, Michelle D, LeBlanc M, Wally J, Zhang Y, Kica G, Karandish S, Arkin CF, Wright DG, Skinner M, McMannis J: Mobilized CD34+ cells selected as autografts in patients with primary light-chain amyloidosis: Rationale and application. [see comment]. Transfusion 38:60–69, 1998PubMedCrossRef Comenzo RL, Michelle D, LeBlanc M, Wally J, Zhang Y, Kica G, Karandish S, Arkin CF, Wright DG, Skinner M, McMannis J: Mobilized CD34+ cells selected as autografts in patients with primary light-chain amyloidosis: Rationale and application. [see comment]. Transfusion 38:60–69, 1998PubMedCrossRef
16.
Zurück zum Zitat Drewinko B, Alexanian R, Boyer H, Barlogie B, Rubinow SI: The growth fraction of human myeloma cells. Blood 57:333–338, 1981PubMed Drewinko B, Alexanian R, Boyer H, Barlogie B, Rubinow SI: The growth fraction of human myeloma cells. Blood 57:333–338, 1981PubMed
17.
Zurück zum Zitat Hamburger A, Salmon SE: Primary bioassay of human myeloma stem cells. J Clin Invest 60:846–854, 1977PubMed Hamburger A, Salmon SE: Primary bioassay of human myeloma stem cells. J Clin Invest 60:846–854, 1977PubMed
18.
Zurück zum Zitat Levy Y, Schmitt C, Tsapis A, Brouet JC, Fermand JP: Phenotype and immunoglobulin gene configuration of blood B cells from patients with multiple myeloma. Clin Exp Immunol 84:435–439, 1991PubMed Levy Y, Schmitt C, Tsapis A, Brouet JC, Fermand JP: Phenotype and immunoglobulin gene configuration of blood B cells from patients with multiple myeloma. Clin Exp Immunol 84:435–439, 1991PubMed
19.
Zurück zum Zitat Guikema JE, Vellenga E, Veeneman JM, Hovenga S, Bakkus MH, Klip H, Bos NA: Multiple myeloma related cells in patients undergoing autologous peripheral blood stem cell transplantation. Br J Haematol 104:748–754, 1999PubMedCrossRef Guikema JE, Vellenga E, Veeneman JM, Hovenga S, Bakkus MH, Klip H, Bos NA: Multiple myeloma related cells in patients undergoing autologous peripheral blood stem cell transplantation. Br J Haematol 104:748–754, 1999PubMedCrossRef
20.
Zurück zum Zitat Billadeau D, Ahmann G, Greipp P, Van Ness B: The bone marrow of multiple myeloma patients contains B cell populations at different stages of differentiation that are clonally related to the malignant plasma cell. J Exp Med 178:1023–1031, 1993PubMedCrossRef Billadeau D, Ahmann G, Greipp P, Van Ness B: The bone marrow of multiple myeloma patients contains B cell populations at different stages of differentiation that are clonally related to the malignant plasma cell. J Exp Med 178:1023–1031, 1993PubMedCrossRef
21.
Zurück zum Zitat Pilarski LM, Masellis-Smith A, Szczepek A, Mant MJ, Belch AR: Circulating clonotypic B cells in the biology of multiple myeloma: Speculations on the origin of myeloma. Leukemia Lymphoma 22:375–383, 1996PubMed Pilarski LM, Masellis-Smith A, Szczepek A, Mant MJ, Belch AR: Circulating clonotypic B cells in the biology of multiple myeloma: Speculations on the origin of myeloma. Leukemia Lymphoma 22:375–383, 1996PubMed
22.
Zurück zum Zitat Mellstedt H, Hammarstrom S, Holm G: Monoclonal lymphocyte population in human plasma cell myeloma. Clin Exp Immunol 17:371–384, 1974PubMed Mellstedt H, Hammarstrom S, Holm G: Monoclonal lymphocyte population in human plasma cell myeloma. Clin Exp Immunol 17:371–384, 1974PubMed
23.
Zurück zum Zitat Epstein J: Myeloma stem cell phenotype. Implications for treatment. Hematol-Oncol Clin North Am 11:43–49, 1997PubMedCrossRef Epstein J: Myeloma stem cell phenotype. Implications for treatment. Hematol-Oncol Clin North Am 11:43–49, 1997PubMedCrossRef
24.
Zurück zum Zitat Berenson JR, Vescio RA, Said J: Multiple myeloma: The cells of origin—a two-way street. Leukemia 12:121–127, 1998PubMedCrossRef Berenson JR, Vescio RA, Said J: Multiple myeloma: The cells of origin—a two-way street. Leukemia 12:121–127, 1998PubMedCrossRef
25.
Zurück zum Zitat Mitterer M, Oduncu F, Lanthaler AJ, Drexler E, Amaddii G, Fabris P, Emmerich B, Coser P, Straka C: The relationship between monoclonal myeloma precursor B cells in the peripheral blood stem cell harvests and the clinical response of multiple myeloma patients.[see comment]. Br J Haematol 106:737–743, 1999PubMedCrossRef Mitterer M, Oduncu F, Lanthaler AJ, Drexler E, Amaddii G, Fabris P, Emmerich B, Coser P, Straka C: The relationship between monoclonal myeloma precursor B cells in the peripheral blood stem cell harvests and the clinical response of multiple myeloma patients.[see comment]. Br J Haematol 106:737–743, 1999PubMedCrossRef
26.
Zurück zum Zitat Davies FE, Rawstron AC, Owen RG, Morgan GJ: Controversies surrounding the clonogenic origin of multiple myeloma.[comment]. Br J Haematol 110:240–241, 2000PubMedCrossRef Davies FE, Rawstron AC, Owen RG, Morgan GJ: Controversies surrounding the clonogenic origin of multiple myeloma.[comment]. Br J Haematol 110:240–241, 2000PubMedCrossRef
27.
Zurück zum Zitat Rawstron AC, Barrans SL, Blythe D, English A, Richards SJ, Fenton JA, Davies FE, Child JA, Jack AS, Morgan GJ: In multiple myeloma, only a single stage of neoplastic plasma cell differentiation can be identified by VLA-5 and CD45 expression.[see comment]. Br J Haematol 113:794–802, 2001PubMedCrossRef Rawstron AC, Barrans SL, Blythe D, English A, Richards SJ, Fenton JA, Davies FE, Child JA, Jack AS, Morgan GJ: In multiple myeloma, only a single stage of neoplastic plasma cell differentiation can be identified by VLA-5 and CD45 expression.[see comment]. Br J Haematol 113:794–802, 2001PubMedCrossRef
28.
Zurück zum Zitat Bergsagel PL, Smith AM, Szczepek A, Mant MJ, Belch AR, Pilarski LM: In multiple myeloma, clonotypic B lymphocytes are detectable among CD19+ peripheral blood cells expressing CD38, CD56, and monotypic Ig light chain.[erratum appears in Blood 1995 Jun 1; 85(11):3365]. Blood 85:436–447, 1995PubMed Bergsagel PL, Smith AM, Szczepek A, Mant MJ, Belch AR, Pilarski LM: In multiple myeloma, clonotypic B lymphocytes are detectable among CD19+ peripheral blood cells expressing CD38, CD56, and monotypic Ig light chain.[erratum appears in Blood 1995 Jun 1; 85(11):3365]. Blood 85:436–447, 1995PubMed
29.
Zurück zum Zitat Rasmussen T, Kastrup J, Knudsen LM, Johnsen HE: High numbers of clonal CD19+ cells in the peripheral blood of a patient with multiple myeloma. Br J Haematol 105:265–267, 1999PubMed Rasmussen T, Kastrup J, Knudsen LM, Johnsen HE: High numbers of clonal CD19+ cells in the peripheral blood of a patient with multiple myeloma. Br J Haematol 105:265–267, 1999PubMed
30.
Zurück zum Zitat Mitterer M, Lanthaler AJ, Schnabel B, Svaldi M, Oduncu F, Coser P, Emmerich B, Huemer H, Straka C: Peripheral blood monoclonal B-cells predict the event free survival in multiple myeloma. Leukemia Lymphoma 41:387–395, 2001PubMed Mitterer M, Lanthaler AJ, Schnabel B, Svaldi M, Oduncu F, Coser P, Emmerich B, Huemer H, Straka C: Peripheral blood monoclonal B-cells predict the event free survival in multiple myeloma. Leukemia Lymphoma 41:387–395, 2001PubMed
31.
Zurück zum Zitat Perfetti V, Ubbiali P, Magni M, Colli Vignarelli M, Casarini S, Matteucci P, Gianni AM, Merlini G: Cells with clonal light chains are present in peripheral blood at diagnosis and in apheretic stem cell harvests of primary amyloidosis. Bone Marrow Transplant 23:323–327, 1999PubMedCrossRef Perfetti V, Ubbiali P, Magni M, Colli Vignarelli M, Casarini S, Matteucci P, Gianni AM, Merlini G: Cells with clonal light chains are present in peripheral blood at diagnosis and in apheretic stem cell harvests of primary amyloidosis. Bone Marrow Transplant 23:323–327, 1999PubMedCrossRef
32.
Zurück zum Zitat Perfetti V, Vignarelli MC, Bellotti V, Glennie MJ, Zorzoli I, Ubbiali P, Obici L, Massa M, Ippoliti G, Ascari E, Merlini G: Membrane CD22 defines circulating myeloma-related cells as mature or later B cells. Lab Invest 77:333–344, 1997PubMed Perfetti V, Vignarelli MC, Bellotti V, Glennie MJ, Zorzoli I, Ubbiali P, Obici L, Massa M, Ippoliti G, Ascari E, Merlini G: Membrane CD22 defines circulating myeloma-related cells as mature or later B cells. Lab Invest 77:333–344, 1997PubMed
33.
Zurück zum Zitat Matsui W, Huff CA, Wang Q, Malehorn MT, Barber J, Tanhehco Y, Smith BD, Civin CI, Jones RJ: Characterization of clonogenic multiple myeloma cells. Blood 103:2332–2336, 2004PubMedCrossRef Matsui W, Huff CA, Wang Q, Malehorn MT, Barber J, Tanhehco Y, Smith BD, Civin CI, Jones RJ: Characterization of clonogenic multiple myeloma cells. Blood 103:2332–2336, 2004PubMedCrossRef
34.
Zurück zum Zitat Vescio RA, Hong CH, Cao J, Kim A, Schiller GJ, Lichtenstein AK, Berenson RJ, Berenson JR: The hematopoietic stem cell antigen, CD34, is not expressed on the malignant cells in multiple myeloma. Blood 84:3283–3290, 1994PubMed Vescio RA, Hong CH, Cao J, Kim A, Schiller GJ, Lichtenstein AK, Berenson RJ, Berenson JR: The hematopoietic stem cell antigen, CD34, is not expressed on the malignant cells in multiple myeloma. Blood 84:3283–3290, 1994PubMed
35.
Zurück zum Zitat Szczepek AJ, Bergsagel PL, Axelsson L, Brown CB, Belch AR, Pilarski LM: CD34+ cells in the blood of patients with multiple myeloma express CD19 and IgH mRNA and have patient-specific IgH VDJ gene rearrangements. Blood 89:1824–1833, 1997PubMed Szczepek AJ, Bergsagel PL, Axelsson L, Brown CB, Belch AR, Pilarski LM: CD34+ cells in the blood of patients with multiple myeloma express CD19 and IgH mRNA and have patient-specific IgH VDJ gene rearrangements. Blood 89:1824–1833, 1997PubMed
36.
Zurück zum Zitat Abraham RS, Geyer SM, Price-Troska TL, Allmer C, Kyle RA, Gertz MA, Fonseca R: Immunoglobulin light chain variable (V) region genes influence clinical presentation and outcome in light chain-associated amyloidosis (AL). Blood 101:3801–3808, 2003PubMedCrossRef Abraham RS, Geyer SM, Price-Troska TL, Allmer C, Kyle RA, Gertz MA, Fonseca R: Immunoglobulin light chain variable (V) region genes influence clinical presentation and outcome in light chain-associated amyloidosis (AL). Blood 101:3801–3808, 2003PubMedCrossRef
37.
Zurück zum Zitat Fais F, Ghiotto F, Hashimoto S, Sellars B, Valetto A, Allen SL, Schulman P, Vinciguerra VP, Rai K, Rassenti LZ, Kipps TJ, Dighiero G, Schroeder Jr HW, Ferrarini M, Chiorazzi N: Chronic lymphocytic leukemia B cells express restricted sets of mutated and unmutated antigen receptors. J Clin Invest 102:1515–1525, 1998PubMedCrossRef Fais F, Ghiotto F, Hashimoto S, Sellars B, Valetto A, Allen SL, Schulman P, Vinciguerra VP, Rai K, Rassenti LZ, Kipps TJ, Dighiero G, Schroeder Jr HW, Ferrarini M, Chiorazzi N: Chronic lymphocytic leukemia B cells express restricted sets of mutated and unmutated antigen receptors. J Clin Invest 102:1515–1525, 1998PubMedCrossRef
38.
Zurück zum Zitat Dunn-Walters D, Belelovsky A, Edelman H, Banerjee M, Mehr R: The dynamics of germinal centre selection as measured by graph-theoretical analysis of mutational lineage trees. Develop Immunol 9:233–245, 2003CrossRef Dunn-Walters D, Belelovsky A, Edelman H, Banerjee M, Mehr R: The dynamics of germinal centre selection as measured by graph-theoretical analysis of mutational lineage trees. Develop Immunol 9:233–245, 2003CrossRef
39.
Zurück zum Zitat Dunn-Walters D, Edelman H, Mehr R: Immune system learning and memory quantified by graphical analysis of B-lymphocyte phylogenetic trees. Bio Sys 76:141–155, 2004 Dunn-Walters D, Edelman H, Mehr R: Immune system learning and memory quantified by graphical analysis of B-lymphocyte phylogenetic trees. Bio Sys 76:141–155, 2004
40.
Zurück zum Zitat Mehr R, Edelman H, Sehgal D, Mage R: Analysis of mutational lineage trees from sites of primary and secondary Ig gene diversification in rabbits and chickens. J Immunol 172:4790–4796, 2004PubMed Mehr R, Edelman H, Sehgal D, Mage R: Analysis of mutational lineage trees from sites of primary and secondary Ig gene diversification in rabbits and chickens. J Immunol 172:4790–4796, 2004PubMed
41.
Zurück zum Zitat Benjamini Y, Hochberg Y: Controlling the false discovery rate: A practical and powerful approach to multiple testing. J Roy Stat Soc 57:289–300, 1995 Benjamini Y, Hochberg Y: Controlling the false discovery rate: A practical and powerful approach to multiple testing. J Roy Stat Soc 57:289–300, 1995
42.
Zurück zum Zitat Lossos IS, Tibshirani R, Narasimhan B, Levy R: The inference of antigen selection on Ig genes. J Immunol 165:5122–5126, 2000PubMed Lossos IS, Tibshirani R, Narasimhan B, Levy R: The inference of antigen selection on Ig genes. J Immunol 165:5122–5126, 2000PubMed
43.
Zurück zum Zitat Kocks C, Rajewsky K: Stepwise intraclonal maturation of antibody affinity through somatic hypermutation. Proc Nat Acad Sci US Am 85:8206–8210, 1988CrossRef Kocks C, Rajewsky K: Stepwise intraclonal maturation of antibody affinity through somatic hypermutation. Proc Nat Acad Sci US Am 85:8206–8210, 1988CrossRef
44.
Zurück zum Zitat Manser T: Evolution of antibody structure during the immune response. The differentiative potential of a single B lymphocyte. J Exp Med 170:1211–1230, 1989PubMedCrossRef Manser T: Evolution of antibody structure during the immune response. The differentiative potential of a single B lymphocyte. J Exp Med 170:1211–1230, 1989PubMedCrossRef
45.
Zurück zum Zitat Jacob J, Kelsoe G, Rajewsky K, Weiss U: Intraclonal generation of antibody mutants in germinal centres. [see comment]. Nature 354:389–392, 1991PubMedCrossRef Jacob J, Kelsoe G, Rajewsky K, Weiss U: Intraclonal generation of antibody mutants in germinal centres. [see comment]. Nature 354:389–392, 1991PubMedCrossRef
46.
Zurück zum Zitat Jacob J, Kelsoe G: In situ studies of the primary immune response to (4-hydroxy-3-nitrophenyl)acetyl. II. A common clonal origin for periarteriolar lymphoid sheath-associated foci and germinal centers. J Exp Med 176:679–687, 1992PubMedCrossRef Jacob J, Kelsoe G: In situ studies of the primary immune response to (4-hydroxy-3-nitrophenyl)acetyl. II. A common clonal origin for periarteriolar lymphoid sheath-associated foci and germinal centers. J Exp Med 176:679–687, 1992PubMedCrossRef
47.
Zurück zum Zitat Shannon M, Mehr R: Reconciling repertoire shift with affinity maturation: The role of deleterious mutations. J Immunol 162:3950–3956, 1999PubMed Shannon M, Mehr R: Reconciling repertoire shift with affinity maturation: The role of deleterious mutations. J Immunol 162:3950–3956, 1999PubMed
48.
Zurück zum Zitat Jacob J, Przylepa J, Miller C, Kelsoe G: In situ studies of the primary immune response to (4-hydroxy-3-nitrophenyl)acetyl. III. The kinetics of V region mutation and selection in germinal center B cells. J Exp Med 178:1293–1307, 1993PubMedCrossRef Jacob J, Przylepa J, Miller C, Kelsoe G: In situ studies of the primary immune response to (4-hydroxy-3-nitrophenyl)acetyl. III. The kinetics of V region mutation and selection in germinal center B cells. J Exp Med 178:1293–1307, 1993PubMedCrossRef
49.
Zurück zum Zitat Banerjee M, Mehr R, Belelovsky A, Spencer J, Dunn-Walters D: Age and tissue-specific differences in human germinal centre B cell selection. Euro J Immunol 32:1947–1957, 2002CrossRef Banerjee M, Mehr R, Belelovsky A, Spencer J, Dunn-Walters D: Age and tissue-specific differences in human germinal centre B cell selection. Euro J Immunol 32:1947–1957, 2002CrossRef
50.
Zurück zum Zitat Shlomchik MJ, Marshak-Rothstein A, Wolfowicz CB, Rothstein TL, Weigert MG: The role of clonal selection and somatic mutation in autoimmunity. Nature 328:805–811, 1987PubMedCrossRef Shlomchik MJ, Marshak-Rothstein A, Wolfowicz CB, Rothstein TL, Weigert MG: The role of clonal selection and somatic mutation in autoimmunity. Nature 328:805–811, 1987PubMedCrossRef
51.
Zurück zum Zitat Kepler TB: Codon bias and plasticity in immunoglobulins. Mole Biol Evol 14:637–643, 1997 Kepler TB: Codon bias and plasticity in immunoglobulins. Mole Biol Evol 14:637–643, 1997
52.
Zurück zum Zitat Dunn-Walters DK, Spencer J: Strong intrinsic biases towards mutation and conservation of bases in human IgVH genes during somatic hypermutation prevent statistical analysis of antigen selection. Immunology 95:339–345, 1998PubMedCrossRef Dunn-Walters DK, Spencer J: Strong intrinsic biases towards mutation and conservation of bases in human IgVH genes during somatic hypermutation prevent statistical analysis of antigen selection. Immunology 95:339–345, 1998PubMedCrossRef
53.
Zurück zum Zitat Berek C: The development of B cells and the B-cell repertoire in the microenvironment of the germinal center. Immunol Rev 126:5–19, 1992PubMedCrossRef Berek C: The development of B cells and the B-cell repertoire in the microenvironment of the germinal center. Immunol Rev 126:5–19, 1992PubMedCrossRef
54.
Zurück zum Zitat Levy R, Levy S, Cleary ML, Carroll W, Kon S, Bird J, Sklar J: Somatic mutation in human B-cell tumors. Immunol Rev 96:43–58, 1987PubMedCrossRef Levy R, Levy S, Cleary ML, Carroll W, Kon S, Bird J, Sklar J: Somatic mutation in human B-cell tumors. Immunol Rev 96:43–58, 1987PubMedCrossRef
55.
Zurück zum Zitat Jacobs H, Bross L: Towards an understanding of somatic hypermutation. Curr Opin Immunol 13:208–218, 2001PubMedCrossRef Jacobs H, Bross L: Towards an understanding of somatic hypermutation. Curr Opin Immunol 13:208–218, 2001PubMedCrossRef
56.
Zurück zum Zitat Perfetti V, Ubbiali P, Vignarelli MC, Diegoli M, Fasani R, Stoppini M, Lisa A, Mangione P, Obici L, Arbustini E, Merlini G: Evidence that amyloidogenic light chains undergo antigen-driven selection. Blood 91:2948–2954, 1998PubMed Perfetti V, Ubbiali P, Vignarelli MC, Diegoli M, Fasani R, Stoppini M, Lisa A, Mangione P, Obici L, Arbustini E, Merlini G: Evidence that amyloidogenic light chains undergo antigen-driven selection. Blood 91:2948–2954, 1998PubMed
57.
Zurück zum Zitat Bakkus MH, Heirman C, Van Riet I, Van Camp B, Thielemans K: Evidence that multiple myeloma Ig heavy chain VDJ genes contain somatic mutations but show no intraclonal variation. Blood 80:2326–2335, 1992PubMed Bakkus MH, Heirman C, Van Riet I, Van Camp B, Thielemans K: Evidence that multiple myeloma Ig heavy chain VDJ genes contain somatic mutations but show no intraclonal variation. Blood 80:2326–2335, 1992PubMed
58.
Zurück zum Zitat Vescio RA, Cao J, Hong CH, Lee JC, Wu CH, Der Danielian M, Wu V, Newman R, Lichtenstein AK, Berenson JR: Myeloma Ig heavy chain V region sequences reveal prior antigenic selection and marked somatic mutation but no intraclonal diversity. J Immunol 155:2487–2497, 1995PubMed Vescio RA, Cao J, Hong CH, Lee JC, Wu CH, Der Danielian M, Wu V, Newman R, Lichtenstein AK, Berenson JR: Myeloma Ig heavy chain V region sequences reveal prior antigenic selection and marked somatic mutation but no intraclonal diversity. J Immunol 155:2487–2497, 1995PubMed
59.
Zurück zum Zitat Taylor BJ, Pittman JA, Seeberger K, Mant MJ, Reiman T, Belch AR, Pilarski LM: Intraclonal homogeneity of clonotypic immunoglobulin M and diversity of nonclinical post-switch isotypes in multiple myeloma: Insights into the evolution of the myeloma clone. Clin Can Res 8:502–513, 2002 Taylor BJ, Pittman JA, Seeberger K, Mant MJ, Reiman T, Belch AR, Pilarski LM: Intraclonal homogeneity of clonotypic immunoglobulin M and diversity of nonclinical post-switch isotypes in multiple myeloma: Insights into the evolution of the myeloma clone. Clin Can Res 8:502–513, 2002
60.
Zurück zum Zitat Kosmas C, Stamatopoulos K, Stavroyianni N, Belessi C, Viniou N, Yataganas X: Molecular analysis of immunoglobulin genes in multiple myeloma. Leukemia Lymphoma 33:253–265, 1999PubMed Kosmas C, Stamatopoulos K, Stavroyianni N, Belessi C, Viniou N, Yataganas X: Molecular analysis of immunoglobulin genes in multiple myeloma. Leukemia Lymphoma 33:253–265, 1999PubMed
61.
Zurück zum Zitat Kuppers R, Klein U, Hansmann ML, Rajewsky K: Cellular origin of human B-cell lymphomas. New England J Med 341:1520–1529, 1999CrossRef Kuppers R, Klein U, Hansmann ML, Rajewsky K: Cellular origin of human B-cell lymphomas. New England J Med 341:1520–1529, 1999CrossRef
62.
Zurück zum Zitat Bahler DW, Levy R: Clonal evolution of a follicular lymphoma: Evidence for antigen selection. Proc Nat Acad Sci US Am 89:6770–6774, 1992CrossRef Bahler DW, Levy R: Clonal evolution of a follicular lymphoma: Evidence for antigen selection. Proc Nat Acad Sci US Am 89:6770–6774, 1992CrossRef
63.
Zurück zum Zitat Matolcsy A, Schattner EJ, Knowles DM, Casali P: Clonal evolution of B cells in transformation from low- to high-grade lymphoma. Euro J Immunol 29:1253–1264, 1999CrossRef Matolcsy A, Schattner EJ, Knowles DM, Casali P: Clonal evolution of B cells in transformation from low- to high-grade lymphoma. Euro J Immunol 29:1253–1264, 1999CrossRef
64.
Zurück zum Zitat Jain R, Roncella S, Hashimoto S, Carbone A, Francia di Celle P, Foa R, Ferrarini M, Chiorazzi N: A potential role for antigen selection in the clonal evolution of Burkitt's lymphoma. J Immunol 153:45–52, 1994PubMed Jain R, Roncella S, Hashimoto S, Carbone A, Francia di Celle P, Foa R, Ferrarini M, Chiorazzi N: A potential role for antigen selection in the clonal evolution of Burkitt's lymphoma. J Immunol 153:45–52, 1994PubMed
65.
Zurück zum Zitat Billadeau D, Blackstadt M, Greipp P, Kyle RA, Oken MM, Kay N, Van Ness B: Analysis of B-lymphoid malignancies using allele-specific polymerase chain reaction: A technique for sequential quantitation of residual disease. Blood 78:3021–3029, 1991PubMed Billadeau D, Blackstadt M, Greipp P, Kyle RA, Oken MM, Kay N, Van Ness B: Analysis of B-lymphoid malignancies using allele-specific polymerase chain reaction: A technique for sequential quantitation of residual disease. Blood 78:3021–3029, 1991PubMed
66.
Zurück zum Zitat Sahota SS, Garand R, Mahroof R, Smith A, Juge-Morineau N, Stevenson FK, Bataille R: V(H) gene analysis of IgM-secreting myeloma indicates an origin from a memory cell undergoing isotype switch events. Blood 94:1070–1076, 1999PubMed Sahota SS, Garand R, Mahroof R, Smith A, Juge-Morineau N, Stevenson FK, Bataille R: V(H) gene analysis of IgM-secreting myeloma indicates an origin from a memory cell undergoing isotype switch events. Blood 94:1070–1076, 1999PubMed
67.
Zurück zum Zitat Sahota SS, Leo R, Hamblin TJ, Stevenson FK: Myeloma VL and VH gene sequences reveal a complementary imprint of antigen selection in tumor cells.[see comment]. Blood 89:219–226, 1997PubMed Sahota SS, Leo R, Hamblin TJ, Stevenson FK: Myeloma VL and VH gene sequences reveal a complementary imprint of antigen selection in tumor cells.[see comment]. Blood 89:219–226, 1997PubMed
68.
Zurück zum Zitat Sahota SS, Leo R, Hamblin TJ, Stevenson FK: Ig VH gene mutational patterns indicate different tumor cell status in human myeloma and monoclonal gammopathy of undetermined significance. Blood 87:746–755, 1996PubMed Sahota SS, Leo R, Hamblin TJ, Stevenson FK: Ig VH gene mutational patterns indicate different tumor cell status in human myeloma and monoclonal gammopathy of undetermined significance. Blood 87:746–755, 1996PubMed
69.
Zurück zum Zitat Szczepek AJ, Seeberger K, Wizniak J, Mant MJ, Belch AR, Pilarski LM: A high frequency of circulating B cells share clonotypic Ig heavy-chain VDJ rearrangements with autologous bone marrow plasma cells in multiple myeloma, as measured by single-cell and in situ reverse transcriptase-polymerase chain reaction. Blood 92:2844–2855, 1998PubMed Szczepek AJ, Seeberger K, Wizniak J, Mant MJ, Belch AR, Pilarski LM: A high frequency of circulating B cells share clonotypic Ig heavy-chain VDJ rearrangements with autologous bone marrow plasma cells in multiple myeloma, as measured by single-cell and in situ reverse transcriptase-polymerase chain reaction. Blood 92:2844–2855, 1998PubMed
70.
Zurück zum Zitat Zaitoun AM: Cell population kinetics of the germinal centres of lymph nodes of BALB/c mice. J Anato 130:131–137, 1980 Zaitoun AM: Cell population kinetics of the germinal centres of lymph nodes of BALB/c mice. J Anato 130:131–137, 1980
71.
Zurück zum Zitat MacLennan IC, Johnson GD, Liu YJ, Gordon J: The heterogeneity of follicular reactions. Res Immunol 142:253–257, 1991PubMedCrossRef MacLennan IC, Johnson GD, Liu YJ, Gordon J: The heterogeneity of follicular reactions. Res Immunol 142:253–257, 1991PubMedCrossRef
72.
Zurück zum Zitat Razzeca KJ, Pillemer E, Weissman IL, Rouse RV: In situ identification of idiotype-positive cells participating in the immune response to phosphorylcholine. Euro J Immunol 16:393–399, 1986 Razzeca KJ, Pillemer E, Weissman IL, Rouse RV: In situ identification of idiotype-positive cells participating in the immune response to phosphorylcholine. Euro J Immunol 16:393–399, 1986
73.
Zurück zum Zitat Abraham RS, Geyer SM, Ramirez-Alvarado M, Price-Troska TL, Gertz MA, Fonseca R: Analysis of somatic hypermutation and antigenic selection in the clonal B cell in immunoglobulin light chain amyloidosis (AL). J Clin Immunol 24:340–353, 2004PubMedCrossRef Abraham RS, Geyer SM, Ramirez-Alvarado M, Price-Troska TL, Gertz MA, Fonseca R: Analysis of somatic hypermutation and antigenic selection in the clonal B cell in immunoglobulin light chain amyloidosis (AL). J Clin Immunol 24:340–353, 2004PubMedCrossRef
74.
Zurück zum Zitat Comenzo RL, Zhang Y, Martinez C, Osman K, Herrera GA: The tropism of organ involvement in primary systemic amyloidosis: Contributions of Ig V(L) germ line gene use and clonal plasma cell burden. Blood 98:714–720, 2001PubMedCrossRef Comenzo RL, Zhang Y, Martinez C, Osman K, Herrera GA: The tropism of organ involvement in primary systemic amyloidosis: Contributions of Ig V(L) germ line gene use and clonal plasma cell burden. Blood 98:714–720, 2001PubMedCrossRef
Metadaten
Titel
Novel Analysis of Clonal Diversification in Blood B Cell and Bone Marrow Plasma Cell Clones in Immunoglobulin Light Chain Amyloidosis
verfasst von
ROSHINI S. ABRAHAM
MICHELLE K. MANSKE
NETA S. ZUCKERMAN
ABHISHEK SOHNI
HANNA EDELMAN
GITIT SHAHAF
MICHAEL M. TIMM
ANGELA DISPENZIERI
MORIE A. GERTZ
RAMIT MEHR
Publikationsdatum
01.01.2007
Erschienen in
Journal of Clinical Immunology / Ausgabe 1/2007
Print ISSN: 0271-9142
Elektronische ISSN: 1573-2592
DOI
https://doi.org/10.1007/s10875-006-9056-9

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