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Immunologic Research

01.12.2009

Insights into the heterogeneity of human B cells: diverse functions, roles in autoimmunity, and use as therapeutic targets

verfasst von: Jennifer H. Anolik, R. John Looney, Frances E. Lund, Troy D. Randall, Iñaki Sanz

Erschienen in: Immunologic Research | Ausgabe 2-3/2009

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Abstract

B cells are critical players in the orchestration of properly regulated immune responses, providing protection against infectious agents without inflicting autoinflammatory damage. A balanced B cell compartment is also essential to create protective immunity in response to vaccines. This difficult compromise is achieved through the finely regulated participation of multiple B cell populations with different antibody-dependent and independent functions. Both types of functions allow B cells to powerfully modulate other components of the innate and adaptive immune system. For the most part, however, the necessary division of labor among different B cell populations is poorly understood. B cell dysfunction has been implicated in multiple autoimmune conditions. The physiological importance and complexity of B cell functions has been brought to the fore in recent years by the success of rituximab-based B cell depletion therapy (BCDT) in multiple autoimmune diseases including rheumatoid arthritis (RA) and multiple sclerosis (MS) which are conventionally viewed as T-cell mediated conditions. Given the widespread utilization of BCDT in malignant and autoimmune diseases and the key role of B cells in both protective immunity and pathogenic autoimmunity, a better understanding of B cell functions is of the essence and a focus of the research in our division. We are investigating these issues through a variety of approaches, including the study of the phenotype and function of human B cell populations in health, their perturbation in autoimmune disease states, the effects of targeted biologic therapies, and the study of relevant murine models.
Literatur
1.
Sanz I, Anolik JH, Looney RJ. B cell depletion therapy in autoimmune diseases. Front Biosci. 2007;12:2546–67.PubMed
2.
Pascual V, Liu YJ, Magalski A, de Bouteiller O, Banchereau J, Capra JD. Analysis of somatic mutation in five B cell subsets of human tonsil. J Exp Med. 1994;180:329–39.PubMed
3.
Sanz I, Wei C, Lee FE-H, Anolik J. Phenotypic and functional heterogeneity of human memory B cells. Semin Immunol. 2008;20:67–82.PubMed
4.
Bohnhorst J, Bjorgan MB, Thoen JE, Natvig JB, Thompson KM. Bm1-bm5 classification of peripheral blood b cells reveals circulating germinal center founder cells in healthy individuals and disturbance in the b cell subpopulations in patients with primary sjogren’s syndrome. J Immunol. 2001;167:3610–8.PubMed
5.
Wei C, Anolik J, Cappione A, Zheng B, Pugh-Bernard A, Brooks J, et al. A new population of cells lacking expression of CD27 represents a notable component of the B cell memory compartment in systemic lupus erythematosus. J Immunol. 2007;178:6624–33.PubMed
6.
Moir S, Malaspina A, Pickeral OK, Donoghue ET, Vasquez J, Miller NJ, et al. Decreased survival of B cells of HIV-viremic patients mediated by altered expression of receptors of the Tnf superfamily. J Exp Med. 2004;200:587–600.
7.
Anolik J, Barnard J, Owen T, Zheng B, Kemshett S, Looney J, et al. Delayed memory B cell recovery in peripheral blood and lymphoid tissue in systemic lupus erythematosus after B cell depletion therapy. Arthritis Rheum. 2007;56:3044–56.PubMed
8.
Cuss AK, Avery DT, Cannons JL, Yu LJ, Nichols KE, Shaw PJ, et al. Expansion of functionally immature transitional B cells is associated with human-immunodeficient states characterized by impaired humoral immunity. J Immunol. 2006;176:1506–16.PubMed
9.
Weller S, Braun MC, Tan BK, Rosenwald A, Cordier C, Conley ME, et al. Human blood IgM “memory” B cells are circulating splenic marginal zone B cells harboring a pre-diversified immunoglobulin repertoire. Blood. 2004;104:3647–54.PubMed
10.
Weller S, Mamani-Matsuda M, Picard C, Cordier C, Lecoeuche D, Gauthier F, et al. Somatic diversification in the absence of antigen-driven responses is the hallmark of the IgM+ IgD+ CD27+ B cell repertoire in infants. J Exp Med. 2008;205:1331–42.PubMed
11.
Tangye SG, Good KL. Human IgM+ CD27+ B cells: memory B cells or “memory” B cells? J Immunol. 2007;179:13–9.PubMed
12.
Anderson SM, Tomayko MM, Shlomchik MJ. Intrinsic properties of human and murine memory B cells. Immunol Rev. 2006;211:280–94.PubMed
13.
Alugupalli KR, Leong JM, Woodland RT, Muramatsu M, Honjo T, Gerstein RM. B1b lymphocytes confer T cell-independent long-lasting immunity. Immunity. 2004;21:379–90.PubMed
14.
Haas KM, Poe JC, Steeber DA, Tedder TF. B-1a and B-1b cells exhibit distinct developmental requirements and have unique functional roles in innate and adaptive immunity to S. pneumoniae. Immunity. 2005;23:7–18.PubMed
15.
Hsu M-C, Toellner K-M, Vinuesa CG, MacLennan ICM. B cell clones that sustain long-term plasmablast growth in T-independent extrafollicular antibody responses. PNAS. 2006;103:5905–10.PubMed
16.
Obukhanych TV, Nussenzweig MC. T-independent type II immune responses generate memory B cells. J Exp Med. 2006;203:305–10.PubMed
17.
Anderson SM, Tomayko MM, Ahuja A, Haberman AM, Shlomchik MJ. New markers for murine memory B cells that define mutated and unmutated subsets. J Exp Med. 2007;204:2103–14.PubMed
18.
Jacobi AM, Reiter K, Mackay M, Aranow C, Hiepe F, Radbruch A, et al. Activated memory B cell subsets correlate with disease activity in systemic lupus erythematosus: delineation by expression of CD27, IgD, and CD95. Arthritis Rheum. 2008;58:1762–73.PubMed
19.
Anolik JH, Barnard J, Cappione A, Pugh-Bernard A, Felgar RE, Looney RJ, et al. Rituximab improves peripheral B cell abnormalities in human systemic lupus erythematosus. Arthritis Rheum. 2004;50:3580–90.PubMed
20.
Wirths S, Lanzavecchia A. ABCB1 transporter discriminates human resting naive B cells from cycling transitional and memory B cells. Eur J Immunol. 2005;35:3433–41.PubMed
21.
Ehrhardt GRA, Hsu JT, Gartland L, Leu C-M, Zhang S, Davis RS, et al. Expression of the immunoregulatory molecule FcRH4 defines a distinctive tissue-based population of memory B cells. J Exp Med. 2005;202:783–91.PubMed
22.
Fecteau JF, Cote G, Neron S. A new memory CD27− IgG+ B cell population in peripheral blood expressing VH genes with low frequency of somatic mutation. J Immunol. 2006;177:3728–36.PubMed
23.
Lund FE. Cytokine-producing B lymphocytes—key regulators of immunity. Curr Opin Immunol. 2008;20:332–8.PubMed
24.
Wojciechowski W, Harris DP, Sprague F, Mousseau B, Makris M, Kusser K, et al. Cytokine-producing effector B cells regulate type 2 immunity to H. polygyrus. Immunity 2009.
25.
Bettelli E, Oukka M, Kuchroo VK. TH-17 cells in the circle of immunity and autoimmunity. Nat Immunol. 2007;8:345–50.PubMed
26.
O’Garra A, Stockinger B, Veldhoen M. Differentiation of human TH-17 cells does require TGF-[beta]!. Nat Immunol. 2008;9:588–90.PubMed
27.
Yamada H, Nakashima Y, Okazaki K, Mawatari T, Fukushi J-I, Kaibara N, et al. Th1 but not Th17 cells predominate in the joints of patients with rheumatoid arthritis. Ann Rheum Dis. 2008;67:1299–304.PubMed
28.
Costantino CM, Baecher-Allan C, Hafler DA. Human regulatory T cells and autoimmunity. Eur J Immunol. 2008;38:921–4.PubMed
29.
Harris DP, Haynes L, Sayles PC, Duso DK, Eaton SM, Lepak NM, et al. Reciprocal regulation of polarized cytokine production by effector B and T cells. Nature Immunology. 2000;1:475–82.PubMed
30.
Harris DP, Goodrich S, Mohrs K, Mohrs M, Lund FE. Cutting edge: the development of IL-4-producing B cells (B effector 2 cells) is controlled by IL-4, IL-4 receptor {alpha}, and Th2 Cells. J Immunol. 2005;175:7103–7.PubMed
31.
Zhong X, Gao W, Degauque N, Bai C, Lu Y, Kenny J, et al. Reciprocal generation of Th1/Th17 and T(reg) cells by B1 and B2 B cells. Eur J Immunol. 2007;37:2400–4.PubMed
32.
Lund FE, Hollifield M, Schuer K, Lines JL, Randall TD, Garvy BA. B cells are required for generation of protective effector and memory CD4 cells in response to pneumocystis lung infection. J Immunol. 2006;176:6147–54.PubMed
33.
Chan OT, Madaio MP, Shlomchik MJ. The central and multiple roles of B cells in lupus pathogenesis. Immunol Rev. 1999;169:107–21.PubMed
34.
Hasegawa M, Hamaguchi Y, Yanaba K, Bouaziz J-D, Uchida J, Fujimoto M, et al. B-lymphocyte depletion reduces skin fibrosis and autoimmunity in the tight-skin mouse model for systemic sclerosis. Am J Pathol. 2006;169:954–66.PubMed
35.
Fillatreau S, Gray D, Anderton SM. Not always the bad guys: B cells as regulators of autoimmune pathology. Nat Rev Immunol. 2008;8:391–7.PubMed
36.
Eynon EE, Parker DC. Small B cells as antigen-presenting cells in the induction of tolerance to soluble protein antigens. J Exp Med. 1992;175:131–8.PubMed
37.
Lampropoulou V, Hoehlig K, Roch T, Neves P, Gomez EC, Sweenie CH, et al. TLR-activated B cells suppress T cell-mediated autoimmunity. J Immunol. 2008;180:4763–73.PubMed
38.
Mizoguchi A, Mizoguchi E, Takedatsu H, Blumberg RS, Bhan AK. Chronic intestinal inflammatory condition generates IL-10-producing regulatory B cell subset characterized by CD1d upregulation. Immunity. 2002;16:219–30.PubMed
39.
Fillatreau S, Sweenie CH, McGeachy MJ, Gray D, Anderton SM. B cells regulate autoimmunity by provision of IL-10. Nat Immunol. 2002;3:944–50.PubMed
40.
Mauri C, Gray D, Mushtaq N, Londei M. Prevention of arthritis by interleukin 10-producing B cells. J Exp Med. 2003;197:489–501.PubMed
41.
Reichardt P, Dornbach B, Rong S, Beissert S, Gueler F, Loser K, et al. Naive B-cells generate regulatory T-cells in the presence of a mature immunologic synapse. Blood. 2007;110:1519–29.PubMed
42.
Wei B, Velazquez P, Turovskaya O, Spricher K, Aranda R, Kronenberg M, et al. Mesenteric B cells centrally inhibit CD4+ T cell colitis through interaction with regulatory T cell subsets. Proceedings of the National Academy of Sciences. 2005;102:2010–5.
43.
Chen X, Jensen PE. Cutting edge: primary B lymphocytes preferentially expand allogeneic FoxP3+ CD4 T Cells. J Immunol. 2007;179:2046–50.PubMed
44.
Mann MK, Maresz K, Shriver LP, Tan Y, Dittel BN. B cell regulation of CD4+ CD25+ T regulatory cells and IL-10 via B7 is essential for recovery from experimental autoimmune encephalomyelitis. J Immunol. 2007;178:3447–56.PubMed
45.
Yanaba K, Bouaziz J-D, Haas KM, Poe JC, Fujimoto M, Tedder TF. A regulatory B cell subset with a unique CD1dhiCD5+ phenotype controls T cell-dependent inflammatory responses. Immunity. 2008;28:639–50.PubMed
46.
Hu C-y, Rodriguez-Pinto D, Du W, Ahuja A, Henegariu O, Wong FS, et al. Treatment with CD20-specific antibody prevents and reverses autoimmune diabetes in mice. J Clin Invest. 2007;117:3857–67.PubMed
47.
Bouaziz JD, Yanaba K, Venturi GM, Wang Y, Tisch RM, Poe JC, et al. Therapeutic B cell depletion impairs adaptive and autoreactive CD4+ T cell activation in mice. Proc Natl Acad Sci USA. 2007;104:20878–83.PubMed
48.
Duan B, Croker BP, Morel L. Lupus resistance is associated with marginal zone abnormalities in an NZM murine model. Lab Invest. 2007;87:14–28.PubMed
49.
Evans JG, Chavez-Rueda KA, Eddaoudi A, Meyer-Bahlburg A, Rawlings DJ, Ehrenstein MR, et al. Novel suppressive function of transitional 2 B cells in experimental arthritis. J Immunol. 2007;178:7868–78.PubMed
50.
Lenert P, Brummel R, Field EH, Ashman RF. TLR-9 activation of marginal zone B cells in lupus mice regulates immunity through increased IL-10 production. J Clin Immunol. 2005;25:29–40.PubMed
51.
Manjarrez-Orduno N, Quach TD, Sanz I. B cells and immunological tolerance. J Invest Dermatol. 2009;129:278–88.PubMed
52.
Youinou P, Devauchelle V, Hutin P, Le Berre R, Saraux A, Pers J-O. A conspicuous role for B cells in sjögren’s syndrome. Clin Rev Allergy Immunol. 2007;32:231–7.PubMed
53.
Duddy M, Niino M, Adatia F, Hebert S, Freedman M, Atkins H, et al. Distinct effector cytokine profiles of memory and naive human B cell subsets and implication in multiple sclerosis. J Immunol. 2007;178:6092–9.PubMed
54.
Schultze JL, Michalak S, Lowne J, Wong A, Gilleece MH, Gribben JG, et al. Human non-germinal center B cell interleukin (IL)-12 production is primarily regulated by T cell signals CD40 ligand, interferon gamma, and IL-10: role of B cells in the maintenance of T cell responses. J Exp Med. 1999;189:1–12.PubMed
55.
Wagner M, Poeck H, Jahrsdoerfer B, Rothenfusser S, Prell D, Bohle B, et al. IL-12p70-dependent Th1 induction by human B cells requires combined activation with CD40 ligand and CpG DNA. J Immunol. 2004;172:954–63.PubMed
56.
Johansson-Lindbom B, Borrebaeck CAK. Germinal center B cells constitute a predominant physiological source of IL-4: implication for Th2 development in vivo. J Immunol. 2002;168:3165–72.PubMed
57.
Kashipaz MR, Huggins ML, Lanyon P, Robins A, Powell RJ, Todd I. Assessment of Be1 and Be2 cells in systemic lupus erythematosus indicates elevated interleukin-10 producing CD5+ B cells. Lupus. 2003;12:356–63.
58.
Malaspina A, Moir S, DiPoto AC, Ho J, Wang W, Roby G, et al. CpG oligonucleotides enhance proliferative and effector responses of B cells in HIV-infected individuals. J Immunol. 2008;181:1199–206.PubMed
59.
Gagro A, Servis D, Cepika A, Toellner KM, Grafton G, Taylor D, et al. Type I cytokine profiles of human naïve and memory B lymphocytes: a potential for memory cells to impact polarization. Immunology. 2006;118:66–77.PubMed
60.
Amu S, Tarkowski A, Dorner T, Bokarewa M, Brisslert M. The human immunomodulatory CD25+ B cell population belongs to the memory B cell pool. Scand J Immunol. 2007;66:77–86.PubMed
61.
Aloisi F, Pujol-Borrell R. Lymphoid neogenesis in chronic inflammatory diseases. Nat Rev Immunol. 2006;6:205–17.PubMed
62.
Weyand CM, Goronzy JJ. Ectopic germinal center formation in rheumatoid synovitis. Ann N Y Acad Sci. 2003;987:140–9.PubMed
63.
Takemura S, Klimiuk PA, Braun A, Goronzy JJ, Weyand CM. T cell activation in rheumatoid synovium is B cell dependent. J Immunol. 2001;167:4710–8.PubMed
64.
Daridon C, Guerrier T, Devauchelle V, Saraux A, Pers JO, Youinou P. Polarization of B effector cells in Sjogren’s syndrome. Autoimmun Rev. 2007;6:427–31.PubMed
65.
Fu Y-X, Huang G, Wang Y, Chaplin DD. B lymphocytes induce the formation of follicular dendritic cell clusters in a lymphotoxin alpha-dependent fashion. J Exp Med. 1998;187:1009–18.PubMed
66.
Angeli V, Ginhoux F, Llodra J, Quemeneur L, Frenette PS, Skobe M, et al. B cell-driven lymphangiogenesis in inflamed lymph nodes enhances dendritic cell mobilization. Immunity. 2006;24:203–15.PubMed
67.
Carragher DM, Rangel-Moreno J, Randall TD. Ectopic lymphoid tissues and local immunity. Semin Immunol. 2008;20:26–42.PubMed
68.
Ansel K, Ngo VN, Hyman P, Luther S, Forster R, Sedgwick JD, et al. A chemokine driven positive feedback loop organizes lymphoid follicles. Nature. 2000;406:309–14.PubMed
69.
Boussiotis VA, Nadler LM, Strominger JL, Goldfeld AE. Tumor necrosis factor alpha is an autocrine growth factor for normal human B cells. Proc Natl Acad Sci USA. 1994;91:7007–11.PubMed
70.
Duddy ME, Alter A, Bar-Or A. Distinct profiles of human B cell effector cytokines: a role in immune regulation? J Immunol. 2004;172:3422–7.PubMed
71.
Anolik JH, Ravikumar R, Barnard J, Owen T, Almudevar A, Milner ECB, et al. Cutting edge: anti-tumor necrosis factor therapy in rheumatoid arthritis inhibits memory B lymphocytes via effects on lymphoid germinal centers and follicular dendritic cell networks. J Immunol. 2008;180:688–92.PubMed
72.
Olson TS, Bamias G, Naganuma M, Rivera-Nieves J, Burcin TL, Ross W, et al. Expanded B cell population blocks regulatory T cells and exacerbates ileitis in a murine model of Crohn disease. J Clin Invest. 2004;114:389–98.PubMed
73.
Edwards JCW, Szczepanski L, Szechinski J, Filipowicz-Sosnowska A, Emery P, Close DR, et al. Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med. 2004;350:2572–81.PubMed
74.
Hauser SL, Waubant E, Arnold DL, Vollmer T, Antel J, Fox RJ, et al. B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. N Engl J Med. 2008;358:676–88.PubMed
75.
Haller MJ, Gottlieb PA, Schatz DA. Type 1 diabetes intervention trials 2007: where are we and where are we going? Curr Opin Endocrinol Diabetes Obes. 2007;14:283–7.PubMed
76.
Golbin JM, Specks U. Part 2: Synopsis of B-lymphocyte targeted therapy of ANCA-associated vasculitis. Clin Exp Rheumatol. 2007;25:74–6.
77.
Devauchelle-Pensec V, Pennec I, Morvan J, Pers J-O, Daridon C, Jousse-Joulin S, et al. Improvement of Sjögren’s syndrome after two infusions of rituximab (anti-CD20). Arthritis Care Res. 2007;57:310–7.
78.
Pers JO, Daridon C, Bendaoud B, Devauchelle V, Berthou C, Saraux A, et al. B-cell depletion and repopulation in autoimmune diseases. Clin Rev Allergy Immunol. 2008;34:50–5.PubMed
79.
Joly P, Mouquet H, Roujeau J-C, D’Incan M, Gilbert D, Jacquot S, et al. A single cycle of rituximab for the treatment of severe pemphigus. N Engl J Med. 2007;357:545–52.PubMed
80.
Isenberg DA. Treating patients with lupus with B-cell depletion. Lupus. 2008;17:400–4.PubMed
81.
Lindholm C, Borjesson-Asp K, Zendjanchi K, Sundqvist AC, Tarkowski A, Bokarewa M. Longterm clinical and immunological effects of anti-CD20 treatment in patients with refractory systemic lupus erythematosus. J Rheumatol. 2008;35:826–33.PubMed
82.
Tokunaga M, Saito K, Kawabata D, Imura Y, Fujii T, Nakayamada S, et al. Efficacy of rituximab (anti-CD20) for refractory systemic lupus erythematosus involving the central nervous system. Ann Rheum Dis. 2007;66:470–5.PubMed
83.
Podolskaya A, Stadermann M, Pilkington C, Marks SD, Tullus K. B-cell depletion therapy for 19 patients with refractory systemic lupus erythematosus. Arch Dis Child. 2008;93:401–6.PubMed
84.
Amoura Z, Mazodier K, Michel M, Viallard J-F, Huong D, Chalumeau N, et al. Efficacy of rituximab in systemic lupus erythematosus: a series of 22 Cases. Arthritis Rheum. 2007;56:S458.
85.
Jonsdottir T, Gunnarsson I, Risselada A, Henriksson EW, Klareskog L, van Vollenhoven RF. Treatment of refractory SLE with rituximab plus cyclophosphamide: clinical effects, serological changes, and predictors of response. Ann Rheum Dis. 2008;67:330–4.PubMed
86.
Eisenberg R, Looney RJ. The therapeutic potential of anti-CD20: “what do B-cells do?”. Clini Immunol. 2005;117:207–13.
87.
Sfikakis PP, Boletis JN, Lionaki S, Vigklis V, Fragiadaki V, Iniotaki A, et al. Remission of proliferative lupus nephritis following B cell depletion therapy is preceded by down-regulation of the T cell costimulatory molecule CD40 ligand: an open-label trial. Arthritis Rheum. 2005;52:501–13.PubMed
88.
Stasi R, Cooper N, Del Poeta G, Stipa E, Laura Evangelista M, Abruzzese E, et al. Analysis of regulatory T cell changes in patients with idiopathic thrombocytopenic purpura receiving B-cell depleting therapy with rituximab. Blood. 2008;112:1147–50.PubMed
89.
McGonagle D, Tan AL, Madden J, Rawstron AC, Rehman A, Emery P, et al. Successful treatment of resistant scleroderma-associated interstitial lung disease with rituximab. Rheumatology (Oxford). 2008;47:552–3.
90.
McFarland HF. The B cell—old player, new position on the team. N Engl J Med. 2008;358:664–5.PubMed
91.
Kavanaugh A, Rosengren S, Lee SJ, Hammaker D, Firestein GS, Kalunian K, et al. Assessment of rituximab’s immunomodulatory synovial effects (ARISE trial). 1: clinical and synovial biomarker results. Ann Rheum Dis. 2008;67:402–8.PubMed
92.
Ng KP, Cambridge G, Leandro MJ, Edwards JC, Ehrenstein M, Isenberg DA. B cell depletion therapy in systemic lupus erythematosus: long term follow up and predictors of response. Ann Rheum Dis. 2007;66:1259–62.PubMed
93.
Looney RJ, Anolik JH, Campbell D, Felgar RE, Young F, Arend LJ, et al. B cell depletion as a novel treatment for systemic lupus erythematosus: a phase I/II dose-escalation trial of rituximab. Arthritis Rheum. 2004;50:2580–9.PubMed
94.
Anolik JH, Friedberg JW, Zheng B, Barnard J, Owen T, Cushing E, et al. B cell reconstitution after rituximab treatment of lymphoma recapitulates B cell ontogeny. Clini Immunol. 2007;122:139–45.
95.
Leandro MJ, Cambridge G, Ehrenstein MR, Edwards JCW. Reconstitution of peripheral blood B cells after depletion with rituximab in patients with rheumatoid arthritis. Arthritis Rheum. 2006;54:613–20.PubMed
96.
Anolik J, Barnard J, Owen T, Dutcher P, Hadley J, Miller C, et al. Restoration of proper germinal center regulation of autoreactive B cells in human SLE after B cell depletion therapy. Arthritis Rheum. 2006;54:S806.
97.
Pugh-Bernard AE, Silverman GJ, Cappione AJ, Villano ME, Ryan DH, Insel RA, et al. Regulation of inherently autoreactive VH4-34 B cells in the maintenance of human B cell tolerance. J Clin Invest. 2001;108:1061–70.PubMed
98.
Cappione AIII, Anolik JH, Pugh-Bernard A, Barnard J, Dutcher P, Silverman G, et al. Germinal center exclusion of autoreactive B cells is defective in human systemic lupus erythematosus. J Clin Invest. 2005;115:3205–16.PubMed
99.
Nicholas MW, Dooley MA, Hogan SL, Anolik J, Looney J, Sanz I, et al. A novel subset of memory B cells is enriched in autoreactivity and correlates with adverse outcomes in SLE. Clinical Immunology. 2008;126:189–201.PubMed
100.
Palanichamy A, Barnard J, Zheng B, Owen T, Quach T, Wei C, et al. Novel human transitional B cell populations revealed by B cell depletion therapy. J Immunol. 2009 (in press).
101.
Lövgren T, Maija-Leena E, Gunnar E, Alm V, Rönnblom L. Induction of interferon-a production in plasmacytoid dendritic cells by immune complexes containing nucleic acid released by necrotic or late apoptotic cells and lupus IgG. Arthritis Rheum. 2004;50:1861–72.PubMed
102.
Pascual V, Banchereau J, Palucka AK. The central role of dendritic cells and interferon-alpha in SLE. Curr Opin Rheumatol. 2003;15:548–56.PubMed
103.
Odendahl M, Jacobi A, Hansen A, Feist E, Hiepe F, Burmester GR, et al. Disturbed peripheral B lymphocyte homeostasis in systemic lupus erythematosus. J Immunol. 2000;165:5970–9.PubMed
104.
Arce E, Jackson DG, Gill MA, Bennett LB, Banchereau J, Pascual V. Increased frequency of pre-germinal center b cells and plasma cell precursors in the blood of children with systemic lupus erythematosus. J Immunol. 2001;167:2361–9.PubMed
105.
Cappione AJ, Pugh-Bernard AE, Anolik JH, Sanz I. Lupus IgG VH4.34 antibodies bind to a 220-kDa glycoform of CD45/B220 on the surface of human B lymphocytes. J Immunol. 2004;172:4298–307.PubMed
106.
Sims GP, Ettinger R, Shirota Y, Yarboro CH, Illei GG, Lipsky PE. Identification and characterization of circulating human transitional B cells. Blood. 2005;105:4390–8.PubMed
107.
Palanichamy A, Barnard J, Owen T, Zheng B, Conley T, Quach T, et al. Characterization of human late transitional B cells: implications for systemic lupus. Arthritis Rheum. 2008;58(9):S.
108.
Mackay M, Stanevsky A, Wang T, Aranow C, Li M, Koenig S, et al. Selective dysregulation of the Fc{gamma}IIB receptor on memory B cells in SLE. J Exp Med. 2006;203:2157–64.PubMed
109.
Hutloff A, Büchner K, Reiter K, Baelde H, Odendahl M, Jacobi A, et al. Involvement of inducible costimulator in the exaggerated memory B cell and plasma cell generation in systemic lupus erythematosus. Arthritis Rheum. 2004;50:3211–20.PubMed
Metadaten
Titel
Insights into the heterogeneity of human B cells: diverse functions, roles in autoimmunity, and use as therapeutic targets
verfasst von
Jennifer H. Anolik
R. John Looney
Frances E. Lund
Troy D. Randall
Iñaki Sanz
Publikationsdatum
01.12.2009
Verlag
Humana Press Inc
Erschienen in
Immunologic Research / Ausgabe 2-3/2009
Print ISSN: 0257-277X
Elektronische ISSN: 1559-0755
DOI
https://doi.org/10.1007/s12026-009-8096-7

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HNO-Op. auch mit über 90?

16.04.2024 HNO-Chirurgie Nachrichten

Mit Blick auf das Risiko für Komplikationen nach elektiven Eingriffen im HNO-Bereich scheint das Alter der Patienten kein ausschlaggebender Faktor zu sein. Entscheidend ist offenbar, wie fit die Betroffenen tatsächlich sind.

Intrakapsuläre Tonsillektomie gewinnt an Boden

16.04.2024 Tonsillektomie Nachrichten

Gegenüber der vollständigen Entfernung der Gaumenmandeln hat die intrakapsuläre Tonsillektomie einige Vorteile, wie HNO-Fachleute aus den USA hervorheben. Sie haben die aktuelle Literatur zu dem Verfahren gesichtet.

Bilateraler Hörsturz hat eine schlechte Prognose

15.04.2024 Hörsturz Nachrichten

Die Mehrzahl der Menschen mit Hörsturz ist einseitig betroffen, doch auch ein beidseitiger Hörsturz ist möglich. Wie häufig solche Fälle sind und wie sich ihr Verlauf darstellt, hat eine HNO-Expertenrunde aus den USA untersucht.

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