Logo of jexpmedHomeThe Rockefeller University PressEditorsContactInstructions for AuthorsThis issue
J Exp Med. 1990 Dec 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. [PMC free article] [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. [PMC free article] [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. [PMC free article] [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


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...