Abstract
The supernatant of unstimulated purified NKH-1 bearing human natural killer (NK) cells was found to enhance ongoing immunoglobulin synthesis. This NK-Cell supernatant (NKSN) enhanced IgE, IgG, and IgA synthesis from corresponding B-cell lines without increasing thymidine incorporation or cell number. Separation of NKH-1+ cells into CD3- or CD3+ cells showed that this activity was produced by the CD3- population. Recombinant human interleukin (IL)-1, IL-2, IL-4, interferon (INF)-beta 1, INF-gamma, granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor (TNF)-alpha, or partially purified low molecular weight B-cell growth factor (BCGF) failed to provide the same enhancement of Ig synthesis. While the NKSN contained small amounts of IL-6 (0.1 U/ml) and IL-6 could increase Ig synthesisin vitro, the optimal IL-6 enhancement was far less than that observed with NKSN. NKSN also enhanced ongoing Ig synthesis fromin vivo activated B cells obtained from peripheral blood or bone marrow but failed to induce Ig synthesis from resting orin vitro activated B cells. These results demonstrate that human NK (CD3-, NKH-1+) cells can produce B-cell differentiation activity capable of regulating Ig productionin vivo, which appears to be distinct from the activity of previously described cytokines.
Similar content being viewed by others
References
Scala G, Allavena P, Djeu JY, Kasahara T, Ortaldo JR, Herbermen RB, Oppenheim JJ: Human large granular lymphocytes are potent producers of interleukin-1. Nature 309:56–59, 1984
Kasahara T, Djeu JY, Dougherty SF, Oppenheim JJ: Capacity of human large granular lymphocytes (LGL) to produce multiple lymphokines: Interleukin 2, interferon, and colony stimulating factor. J Immunol 131:2379–2385, 1983
Pistoia V, Cozzolino F, Torcia M, Castigli E, Ferrarini M: Production of B cell growth factor by a leu-7+, OKMI+ non-T cell with the features of large granular lymphocytes (LGL). J Immunol 134:3179–3184, 1985
Vyakarnam A, Brenner MK, Reittie JE, Houlker CH, Lachmann PJ: Human clones with natural killer functions can activate B cells and secrete B cell differentiation factors. Eur J Immunol 15:606–610, 1985
Kimata H, Shanahan F, Brogan M, Targan S, Saxon A: Modulation of ongoing human immunoglobulin synthesis by natural killer cells. Cell Immunol 107:74–88, 1987
Boyum A: Isolation of mononuclear cells and granulocytes from human blood. Scan J Clin Lab Invest 97(Suppl):77–89, 1968
Saxon A, Feldhaus JL, Robins RA: Single step separation of human T and B cells using AET-treated SRBC rosette. J Immunol Methods 12:285–288, 1976
Sherr EH, Stein LD, Dosch HM, Saxon A: IgE-enhancing activity directly and selectively affects activated B cells: Evidence for a human IgE differentiation factor. J Immunol 138:3836–3843, 1987
Wysocki LJ, Sato UL: “Panning” for lymphocytes. A method for cell selection. Proc Natl Acad Sci USA 75:2844–2848, 1978
Perussia B, Acuto O, Terhost C, Faust J, Lazarus R, Fanning V, Trinchieri G: Human natural killer cells analyzed by B73.1, a monoclonal antibody blocking Fc receptor functions. II. Studies of B73.1 antibody-antigen interaction on the lymphocyte membrane. J Immunol 130:2144–2148, 1983
Hercend T, Griffin JD, Bensussan A, Schmidt RE, Elson MA, Brennan A, Murry C, Dalet JF, Schlosman SF: Generation of monoclonal antibodies to a human natural killer clones: Characterization of the NK-associated antigen, NKH-1 (200KD) and NKH-2 (60KD) expressed on subsets of large granular lymphocytes. J Clin Invest 75:932–943, 1985
Yodoi J, Ishizaka T, Ishizaka K: Lymphocyte bearing Fc receptors for IgE. II. Induction of FcE-receptor bearing rat lymphocytes by IgE. J Immunol 123:455–462, 1979
Hirano T, Taga T, Nakano N, Yasukawa K, Kashiwamura S, Shimizu K, Nakajima K, Pyun KH, Kishimoto T: Purification to homogeneity and characterization of human B-cell differentiation factor (BCDF or BSFp-2). Proc Natl Acad Sci USA 82:5490–5494, 1985
Hassner A, Saxon A: Isotype-specific human suppressor T cells for IgE synthesis activated by IgE-anti-IgE immune complexes. J Immunol 132:2844–2849, 1984
Merrill JE, Mohldtrom C, Uittenbogaart C, Kermani-Arab V, Ellison GW, Myers LW: Response to and production of interleukin 2 by peripheral blood and cerebrospinal fluid lymphocytes of patients with multiple sclerosis. J Immunol 133:1931–1937, 1984
Lanier LL, Le AM, Civin CI, Loken MR, Philips JH: The relationship of CD16 (Leu-11) and Leu-19 (NKH-1) antigen expression on human peripheral blood NK cells and cytotoxic T lymphocytes. J Immunol 136:4480–4486, 1986
Wright SC, Bonavida B: Studies of the mechanisms of natural killer cell-mediated cytotoxicity. VII. Functional comparison of human natural killer cytotoxic factors with recombinant lymphotoxin and tumor necrosis factor. J Immunol 138:1791–1798, 1987
Nakagawa T, Nakagawa N, Volkman DJ, Fauci AS: Sequential synergistic effect of interleukin 2 and interferon-gamma on the differentiation of a Tac-antigen-positive B cell line. J Immunol 136:164–168, 1986
Le J, Lin Jian-Xin, Henriksen-Destefano D, Vilcek J: Bacterial lipopolysaccharide-induced interferon-gamma production: Roles of interleukin 1 and interleukin 2. J Immunol 136:4525–4530, 1986
Jelink DF, Lipsky PE: Enhancement of human B cell proliferation and differentiation by tumor necrosis-alpha and interleukin 1. J Immunol 139:2970–2976, 1987
Targan S, Brevia J, Newman W, Stevens RH: Is the NK lytic process involved in the mechanism of NK suppression of antibody-producing cells? J Immunol 134:666–669, 1985
Procopio ADG, Allavena P, Ortaldo JR: Noncytotoxic functions of natural killer (NK) cells: Large granular lymphocytes (LGL) produce a B cell growth factor (BCGF). J Immunol 135:3264–3271, 1985
Robles CP, Pollack SB: Regulation of the secondary in vitro antibody response by endogenous natural killer cells: Kinetics, isotype preference, and non-identity with suppressor T cells. J Immunol 137:2418–2424, 1986
Brenner M, Reittie JE, Grob J-P, Wimperis JZ, Stepeens S, Patterson J, Hoffbrand AV, Prentice HG: The contribution of large granular lymphocytes to B cell activation and differentiation after T-cell-depleted allogeneic bone marrow transplantation. Transplantation 42:257–261, 1986
Rodriguez NA, Blanca I, Baroja ML, Arama S, Leon-Ponte M, Abadi I, Bianco NE: Helper activity by human large granular lymphocytes in in vitro immunoglobulin synthesis. J Clin Immunol 7:356–364, 1987
Azuma C, Tanabe T, Konoshi T, Noma T, Matsuda F, Yaoita Y, Takasu K, Hammarstrom L, Smith CIE, Saverinson E, Honjo T: Cloning of cDNA for human T-cell replacing factor (interleukin 5) and comparison with the murine homologue. Nucleic Acids Res 14:9149–9158, 1986
De la Sen ML, Garcia-Alonso A, Brieva JA: Human B lymphocytes capable of spontaneous Ig production in short-term cultures. II. Relationship with the spontaneous DNA-synthesizing B cells. Cell Immunol 104:281–289, 1987
Brenner MK, Vyjarnam A, Reittie JE, Wimperis JZ, Grob JP, Hoffbrand AV, Prentice HG: Human large granular lymphocyte induce immunoglobulin synthesis after bone marrow transplantation. Eur J Immunol 17:443–47, 1987
Kimata H, Saxon A: Induction and function of natural killer cells with receptors for IgE and IgA by immune complexes. J Clin Invest 82:160–167, 1988
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kimata, H., Sherr, E.H. & Saxon, A. Human natural killer (NK) cells produce a late-acting B-cell differentiation activity. J Clin Immunol 8, 381–389 (1988). https://doi.org/10.1007/BF00917154
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00917154