Search tips
Search criteria 


Logo of jexpmedHomeThe Rockefeller University PressEditorsContactInstructions for AuthorsThis issue
J Exp Med. 1990 December 1; 172(6): 1625–1631.
PMCID: PMC2188770

Interleukin 10, a novel B cell stimulatory factor: unresponsiveness of X chromosome-linked immunodeficiency B cells


Highly purified, small dense splenic B cells from unstimulated mice showed increased expression of class II major histocompatibility complex (MHC) antigens and enhanced viability when cultured with affinity-purified recombinant interleukin 10 (rIL-10), compared with B cells cultured in medium alone. These responses were blocked by a monoclonal antibody (mAb) specific for IL-10, but not by an isotype- matched control antibody. IL-10 did not upregulate the expression of Fc epsilon receptors (CD23) or class I MHC antigens on small dense B cells or induce their replication as monitored by [3H]thymidine incorporation. While these B cell-stimulatory properties of IL-10 are also mediated by IL-4, the two cytokines appear to act independently in these assays; anti-IL-10 antibodies blocked IL-10 but not IL-4-mediated B cell viability enhancement, and vice versa. Similarly, since IL-4 upregulates CD23 on small dense B cells, the inability of IL-10 to do so argues against its acting via endogenously generated IL-4. Finally, IL-10 did not upregulate class II MHC antigens on B cells from X chromosome-linked immunodeficiency (XID) mice, while the same cells showed normal upregulation of class II antigens in response to IL-4. This report also extends our understanding of the relationship between IL-10 and the highly homologous Epstein-Barr virus (EBV)-encoded Bam HI fragment C rightward reading frame no. 1 (BCRFI) protein. It has previously been shown that BCRFI protein exhibits the cytokine synthesis inhibitory activity of IL-10. This report indicates that BCRFI protein also enhances in vitro B cell viability, but does not upregulate class II MHC antigens on B cells. One explanation for these data is that IL-10 contains at least two functional epitopes, only one of which has been conserved by EBV.

Full Text

The Full Text of this article is available as a PDF (841K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Howard M, Paul WE. Regulation of B-cell growth and differentiation by soluble factors. Annu Rev Immunol. 1983;1:307–333. [PubMed]
  • Kishimoto T, Hirano T. Molecular regulation of B lymphocyte response. Annu Rev Immunol. 1988;6:485–512. [PubMed]
  • O'Garra A, Umland S, De France T, Christiansen J. 'B-cell factors' are pleiotropic. Immunol Today. 1988 Feb;9(2):45–54. [PubMed]
  • Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol. 1986 Apr 1;136(7):2348–2357. [PubMed]
  • O'Garra A, Stapleton G, Dhar V, Pearce M, Schumacher J, Rugo H, Barbis D, Stall A, Cupp J, Moore K, et al. Production of cytokines by mouse B cells: B lymphomas and normal B cells produce interleukin 10. Int Immunol. 1990;2(9):821–832. [PubMed]
  • Suda T, O'Garra A, MacNeil I, Fischer M, Bond MW, Zlotnik A. Identification of a novel thymocyte growth-promoting factor derived from B cell lymphomas. Cell Immunol. 1990 Aug;129(1):228–240. [PubMed]
  • Moore KW, Vieira P, Fiorentino DF, Trounstine ML, Khan TA, Mosmann TR. Homology of cytokine synthesis inhibitory factor (IL-10) to the Epstein-Barr virus gene BCRFI. Science. 1990 Jun 8;248(4960):1230–1234. [PubMed]
  • Ohara J, Paul WE. Production of a monoclonal antibody to and molecular characterization of B-cell stimulatory factor-1. Nature. 1985 May 23;315(6017):333–336. [PubMed]
  • van Kimmenade A, Bond MW, Schumacher JH, Laquoi C, Kastelein RA. Expression, renaturation and purification of recombinant human interleukin 4 from Escherichia coli. Eur J Biochem. 1988 Apr 5;173(1):109–114. [PubMed]
  • Lowenthal JW, Castle BE, Christiansen J, Schreurs J, Rennick D, Arai N, Hoy P, Takebe Y, Howard M. Expression of high affinity receptors for murine interleukin 4 (BSF-1) on hemopoietic and nonhemopoietic cells. J Immunol. 1988 Jan 15;140(2):456–464. [PubMed]
  • Umland SP, Go NF, Cupp JE, Howard M. Responses of B cells from autoimmune mice to IL-5. J Immunol. 1989 Mar 1;142(5):1528–1535. [PubMed]
  • Rao M, Lee WT, Conrad DH. Characterization of a monoclonal antibody directed against the murine B lymphocyte receptor for IgE. J Immunol. 1987 Mar 15;138(6):1845–1851. [PubMed]
  • Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983 Dec 16;65(1-2):55–63. [PubMed]
  • Roehm NW, Leibson HJ, Zlotnik A, Kappler J, Marrack P, Cambier JC. Interleukin-induced increase in Ia expression by normal mouse B cells. J Exp Med. 1984 Sep 1;160(3):679–694. [PMC free article] [PubMed]
  • Noelle R, Krammer PH, Ohara J, Uhr JW, Vitetta ES. Increased expression of Ia antigens on resting B cells: an additional role for B-cell growth factor. Proc Natl Acad Sci U S A. 1984 Oct;81(19):6149–6153. [PubMed]
  • Alderson MR, Pike BL, Nossal GJ. Single cell studies on the role of B-cell stimulatory factor 1 in B-cell activation. Proc Natl Acad Sci U S A. 1987 Mar;84(5):1389–1393. [PubMed]
  • Hudak SA, Gollnick SO, Conrad DH, Kehry MR. Murine B-cell stimulatory factor 1 (interleukin 4) increases expression of the Fc receptor for IgE on mouse B cells. Proc Natl Acad Sci U S A. 1987 Jul;84(13):4606–4610. [PubMed]
  • Kikutani H, Suemura M, Owaki H, Nakamura H, Sato R, Yamasaki K, Barsumian EL, Hardy RR, Kishimoto T. Fc epsilon receptor, a specific differentiation marker transiently expressed on mature B cells before isotype switching. J Exp Med. 1986 Nov 1;164(5):1455–1469. [PMC free article] [PubMed]
  • Defrance T, Aubry JP, Rousset F, Vanbervliet B, Bonnefoy JY, Arai N, Takebe Y, Yokota T, Lee F, Arai K, et al. Human recombinant interleukin 4 induces Fc epsilon receptors (CD23) on normal human B lymphocytes. J Exp Med. 1987 Jun 1;165(6):1459–1467. [PMC free article] [PubMed]
  • Scher I. CBA/N immune defective mice; evidence for the failure of a B cell subpopulation to be expressed. Immunol Rev. 1982;64:117–136. [PubMed]
  • Hayakawa K, Hardy RR, Herzenberg LA. Peritoneal Ly-1 B cells: genetic control, autoantibody production, increased lambda light chain expression. Eur J Immunol. 1986 Apr;16(4):450–456. [PubMed]
  • Leclercq L, Cambier JC, Mishal Z, Julius MH, Theze J. Supernatant from a cloned helper T cell stimulates most small resting B cells to undergo increased I-A expression, blastogenesis, and progression through cell cycle. J Immunol. 1986 Jan;136(2):539–545. [PubMed]
  • Ono S, Hayashi S, Takahama Y, Dobashi K, Katoh Y, Nakanishi K, Paul WE, Hamaoka T. Identification of two distinct factors, B151-TRF1 and B151-TRF2, inducing differentiation of activated B cells and small resting B cells into antibody-producing cells. J Immunol. 1986 Jul 1;137(1):187–196. [PubMed]
  • Cross D, Cambier JC. Transforming growth factor beta 1 has differential effects on B cell proliferation and activation antigen expression. J Immunol. 1990 Jan 15;144(2):432–439. [PubMed]
  • Steeg PS, Moore RN, Johnson HM, Oppenheim JJ. Regulation of murine macrophage Ia antigen expression by a lymphokine with immune interferon activity. J Exp Med. 1982 Dec 1;156(6):1780–1793. [PMC free article] [PubMed]
  • Zlotnik A, Shimonkevitz RP, Gefter ML, Kappler J, Marrack P. Characterization of the gamma-interferon-mediated induction of antigen-presenting ability in P388D1 cells. J Immunol. 1983 Dec;131(6):2814–2820. [PubMed]
  • Mond JJ, Carman J, Sarma C, Ohara J, Finkelman FD. Interferon-gamma suppresses B cell stimulation factor (BSF-1) induction of class II MHC determinants on B cells. J Immunol. 1986 Dec 1;137(11):3534–3537. [PubMed]
  • Oliver K, Krammer PH, Tucker PW, Vitetta ES. The effects of cytokines and adherent cells on the interleukin 4-mediated induction of Ia antigens on resting B cells. Cell Immunol. 1987 May;106(2):428–436. [PubMed]
  • Hasler F, Bluestein HG, Zvaifler NJ, Epstein LB. Analysis of the defects responsible for the impaired regulation of Epstein-Barr virus-induced B cell proliferation by rheumatoid arthritis lymphocytes. I. Diminished gamma interferon production in response to autologous stimulation. J Exp Med. 1983 Jan 1;157(1):173–188. [PMC free article] [PubMed]
  • Lotz M, Tsoukas CD, Fong S, Carson DA, Vaughan JH. Regulation of Epstein-Barr virus infection by recombinant interferons. Selected sensitivity to interferon-gamma. Eur J Immunol. 1985 May;15(5):520–525. [PubMed]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press