Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1994 Jul;94(1):97–104. doi: 10.1172/JCI117354

Interleukin 10 induces B lymphocytes from IgA-deficient patients to secrete IgA.

F Brière 1, J M Bridon 1, D Chevet 1, G Souillet 1, F Bienvenu 1, C Guret 1, H Martinez-Valdez 1, J Banchereau 1
PMCID: PMC296286  PMID: 7518836

Abstract

We have previously shown that human B lymphocytes cultured in the CD40 system, composed of an anti-CD40 mAb presented by a CD32-transfected fibroblastic cell line, proliferate but do not secrete antibodies. However, the addition of particles of Staphylococcus aureus Cowan (SAC) induces B cell differentiation even in the absence of exogenous cytokines (CD40/SAC system). Additionally, B lymphocytes cultured in the CD40 system in the presence of human IL-10, produce IgM, IgG, and IgA, and Ig levels are further increased by SAC. Here, we have studied the capacity of peripheral blood lymphocytes from patients with IgA deficiency (IgA-D) to secrete Igs, particularly IgA after CD40 triggering. Peripheral blood mononuclear cells (PBMNC) from IgA-D patients cultured in the CD40/SAC system produced IgM and IgG, but not IgA. The addition of IL-10 to the cultures, enhanced the production of IgM and IgG and most strikingly induced the production of high amounts of IgA. The addition of IL-10 to PBMNC from IgA-D patients activated through CD40 alone resulted in the production of IgA. Thus, SAC and anti-CD40 mAb stimulate B cells to differentiate into cells secreting IgG and IgM whereas IL-10 plays a central role in inducing B cells from IgA-D patients to differentiate into IgA secreting cells.

Full text

PDF
103

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Allen R. C., Armitage R. J., Conley M. E., Rosenblatt H., Jenkins N. A., Copeland N. G., Bedell M. A., Edelhoff S., Disteche C. M., Simoneaux D. K. CD40 ligand gene defects responsible for X-linked hyper-IgM syndrome. Science. 1993 Feb 12;259(5097):990–993. doi: 10.1126/science.7679801. [DOI] [PubMed] [Google Scholar]
  2. Armitage R. J., Sato T. A., Macduff B. M., Clifford K. N., Alpert A. R., Smith C. A., Fanslow W. C. Identification of a source of biologically active CD40 ligand. Eur J Immunol. 1992 Aug;22(8):2071–2076. doi: 10.1002/eji.1830220817. [DOI] [PubMed] [Google Scholar]
  3. Aruffo A., Farrington M., Hollenbaugh D., Li X., Milatovich A., Nonoyama S., Bajorath J., Grosmaire L. S., Stenkamp R., Neubauer M. The CD40 ligand, gp39, is defective in activated T cells from patients with X-linked hyper-IgM syndrome. Cell. 1993 Jan 29;72(2):291–300. doi: 10.1016/0092-8674(93)90668-g. [DOI] [PubMed] [Google Scholar]
  4. Aucouturier P., Mariault M., Lacombe C., Preud'homme J. L. Frequency of selective IgG subclass deficiency: a reappraisal. Clin Immunol Immunopathol. 1992 Jun;63(3):289–291. doi: 10.1016/0090-1229(92)90236-h. [DOI] [PubMed] [Google Scholar]
  5. Banchereau J., de Paoli P., Vallé A., Garcia E., Rousset F. Long-term human B cell lines dependent on interleukin-4 and antibody to CD40. Science. 1991 Jan 4;251(4989):70–72. doi: 10.1126/science.1702555. [DOI] [PubMed] [Google Scholar]
  6. Bendtzen K., Svenson M., Jønsson V., Hippe E. Autoantibodies to cytokines--friends or foes? Immunol Today. 1990 May;11(5):167–169. doi: 10.1016/0167-5699(90)90068-k. [DOI] [PubMed] [Google Scholar]
  7. Brière F., Servet-Delprat C., Bridon J. M., Saint-Remy J. M., Banchereau J. Human interleukin 10 induces naive surface immunoglobulin D+ (sIgD+) B cells to secrete IgG1 and IgG3. J Exp Med. 1994 Feb 1;179(2):757–762. doi: 10.1084/jem.179.2.757. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Burdin N., Péronne C., Banchereau J., Rousset F. Epstein-Barr virus transformation induces B lymphocytes to produce human interleukin 10. J Exp Med. 1993 Feb 1;177(2):295–304. doi: 10.1084/jem.177.2.295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cassidy J. T., Oldham G., Platts-Mills T. A. Functional assessment of a B cell defect in patients with selective IgA deficiency. Clin Exp Immunol. 1979 Feb;35(2):296–305. [PMC free article] [PubMed] [Google Scholar]
  10. Chevet D., Rifle G., Guiguet M., Chalopin J. M., Tanter Y., Mousson C., Rebibou J. M. Acquired selective immunoglobulin A deficiency in renal transplant recipients. Transplant Proc. 1993 Feb;25(1 Pt 2):1355–1358. [PubMed] [Google Scholar]
  11. Chomarat P., Rissoan M. C., Banchereau J., Miossec P. Interferon gamma inhibits interleukin 10 production by monocytes. J Exp Med. 1993 Feb 1;177(2):523–527. doi: 10.1084/jem.177.2.523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Chrétien I., Pène J., Brière F., De Waal Malefijt R., Rousset F., De Vries J. E. Regulation of human IgE synthesis. I. Human IgE synthesis in vitro is determined by the reciprocal antagonistic effects of interleukin 4 and interferon-gamma. Eur J Immunol. 1990 Feb;20(2):243–251. doi: 10.1002/eji.1830200203. [DOI] [PubMed] [Google Scholar]
  13. Conley M. E., Cooper M. D. Immature IgA B cells in IgA-deficient patients. N Engl J Med. 1981 Aug 27;305(9):495–497. doi: 10.1056/NEJM198108273050905. [DOI] [PubMed] [Google Scholar]
  14. Defrance T., Vanbervliet B., Aubry J. P., Takebe Y., Arai N., Miyajima A., Yokota T., Lee F., Arai K., de Vries J. E. B cell growth-promoting activity of recombinant human interleukin 4. J Immunol. 1987 Aug 15;139(4):1135–1141. [PubMed] [Google Scholar]
  15. Defrance T., Vanbervliet B., Brière F., Durand I., Rousset F., Banchereau J. Interleukin 10 and transforming growth factor beta cooperate to induce anti-CD40-activated naive human B cells to secrete immunoglobulin A. J Exp Med. 1992 Mar 1;175(3):671–682. doi: 10.1084/jem.175.3.671. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. DiSanto J. P., Bonnefoy J. Y., Gauchat J. F., Fischer A., de Saint Basile G. CD40 ligand mutations in x-linked immunodeficiency with hyper-IgM. Nature. 1993 Feb 11;361(6412):541–543. doi: 10.1038/361541a0. [DOI] [PubMed] [Google Scholar]
  17. Favre C., Wijdenes J., Cabrillat H., Djossou O., Banchereau J., de Vries J. E. Epitope mapping of recombinant human gamma interferon using monoclonal antibodies. Mol Immunol. 1989 Jan;26(1):17–25. doi: 10.1016/0161-5890(89)90015-1. [DOI] [PubMed] [Google Scholar]
  18. Fong Y., Tracey K. J., Moldawer L. L., Hesse D. G., Manogue K. B., Kenney J. S., Lee A. T., Kuo G. C., Allison A. C., Lowry S. F. Antibodies to cachectin/tumor necrosis factor reduce interleukin 1 beta and interleukin 6 appearance during lethal bacteremia. J Exp Med. 1989 Nov 1;170(5):1627–1633. doi: 10.1084/jem.170.5.1627. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Inoue T., Okubo H., Kudo J., Ikuta T., Hachimine K., Shibata R., Yoshinari O., Fukada K., Yanase T. Selective IgA deficiency: analysis of Ig production in vitro. J Clin Immunol. 1984 May;4(3):235–241. doi: 10.1007/BF00914971. [DOI] [PubMed] [Google Scholar]
  20. Ishida H., Hastings R., Thompson-Snipes L., Howard M. Modified immunological status of anti-IL-10 treated mice. Cell Immunol. 1993 May;148(2):371–384. doi: 10.1006/cimm.1993.1119. [DOI] [PubMed] [Google Scholar]
  21. Islam K. B., Nilsson L., Sideras P., Hammarström L., Smith C. I. TGF-beta 1 induces germ-line transcripts of both IgA subclasses in human B lymphocytes. Int Immunol. 1991 Nov;3(11):1099–1106. doi: 10.1093/intimm/3.11.1099. [DOI] [PubMed] [Google Scholar]
  22. Korthäuer U., Graf D., Mages H. W., Brière F., Padayachee M., Malcolm S., Ugazio A. G., Notarangelo L. D., Levinsky R. J., Kroczek R. A. Defective expression of T-cell CD40 ligand causes X-linked immunodeficiency with hyper-IgM. Nature. 1993 Feb 11;361(6412):539–541. doi: 10.1038/361539a0. [DOI] [PubMed] [Google Scholar]
  23. Mitsuya H., Tomino S., Hisamitsu S., Kishimoto S. Evidence for the failure of IgA specific T helper activity in a patient with immunodeficiency with hyper IgM. J Clin Lab Immunol. 1979 Nov;2(4):337–342. [PubMed] [Google Scholar]
  24. Nonoyama S., Farrington M., Ishida H., Howard M., Ochs H. D. Activated B cells from patients with common variable immunodeficiency proliferate and synthesize immunoglobulin. J Clin Invest. 1993 Sep;92(3):1282–1287. doi: 10.1172/JCI116701. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Panem S., Check I. J., Henriksen D., Vilcek J. Antibodies to alpha-interferon in a patient with systemic lupus erythematosus. J Immunol. 1982 Jul;129(1):1–3. [PubMed] [Google Scholar]
  26. Peltz G. A., Trounstine M. L., Moore K. W. Cloned and expressed human Fc receptor for IgG mediates anti-CD3-dependent lymphoproliferation. J Immunol. 1988 Sep 15;141(6):1891–1896. [PubMed] [Google Scholar]
  27. Plebani A., Ugazio A. G., Avanzini M. A., Massimi P., Zonta L., Monafo V., Burgio G. R. Serum IgG subclass concentrations in healthy subjects at different age: age normal percentile charts. Eur J Pediatr. 1989 Dec;149(3):164–167. doi: 10.1007/BF01958271. [DOI] [PubMed] [Google Scholar]
  28. Rousset F., Garcia E., Banchereau J. Cytokine-induced proliferation and immunoglobulin production of human B lymphocytes triggered through their CD40 antigen. J Exp Med. 1991 Mar 1;173(3):705–710. doi: 10.1084/jem.173.3.705. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Rousset F., Garcia E., Defrance T., Péronne C., Vezzio N., Hsu D. H., Kastelein R., Moore K. W., Banchereau J. Interleukin 10 is a potent growth and differentiation factor for activated human B lymphocytes. Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1890–1893. doi: 10.1073/pnas.89.5.1890. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Schaffer F. M., Monteiro R. C., Volanakis J. E., Cooper M. D. IgA deficiency. Immunodefic Rev. 1991;3(1):15–44. [PubMed] [Google Scholar]
  31. Spriggs M. K., Armitage R. J., Strockbine L., Clifford K. N., Macduff B. M., Sato T. A., Maliszewski C. R., Fanslow W. C. Recombinant human CD40 ligand stimulates B cell proliferation and immunoglobulin E secretion. J Exp Med. 1992 Dec 1;176(6):1543–1550. doi: 10.1084/jem.176.6.1543. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Vallé A., Zuber C. E., Defrance T., Djossou O., De Rie M., Banchereau J. Activation of human B lymphocytes through CD40 and interleukin 4. Eur J Immunol. 1989 Aug;19(8):1463–1467. doi: 10.1002/eji.1830190818. [DOI] [PubMed] [Google Scholar]
  33. Volanakis J. E., Zhu Z. B., Schaffer F. M., Macon K. J., Palermos J., Barger B. O., Go R., Campbell R. D., Schroeder H. W., Jr, Cooper M. D. Major histocompatibility complex class III genes and susceptibility to immunoglobulin A deficiency and common variable immunodeficiency. J Clin Invest. 1992 Jun;89(6):1914–1922. doi: 10.1172/JCI115797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Waldmann T. A., Broder S., Krakauer R., Durm M., Meade B., Goldman C. Defect in IgA secretion and in IgA specific suppressor cells in patients with selective IgA deficiency. Trans Assoc Am Physicians. 1976;89:215–224. [PubMed] [Google Scholar]
  35. Wilton A. N., Cobain T. J., Dawkins R. L. Family studies of IgA deficiency. Immunogenetics. 1985;21(4):333–342. doi: 10.1007/BF00430799. [DOI] [PubMed] [Google Scholar]
  36. Zielen S., Bauscher P., Hofmann D., Meuer S. C. Interleukin 10 and immune restoration in common variable immunodeficiency. Lancet. 1993 Sep 18;342(8873):750–751. [PubMed] [Google Scholar]
  37. Zielen S., Sehrt P., Rahmig J., Hofmann D., Brière F., Meuer S. C. Rekonstitution der Immunglobulinproduktion bei Patienten mit variablem Immundefektsyndrom (CVI) durch das CD40-System und IL-10. Immun Infekt. 1994 Feb;22(1):24–25. [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES