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. 1992 Aug;89(2):223–229. doi: 10.1111/j.1365-2249.1992.tb06936.x

IL-4 down-regulates the surface expression of CD5 on B cells and inhibits spontaneous immunoglobulin and IgM-rheumatoid factor production in patients with rheumatoid arthritis.

T Hidaka 1, A Kitani 1, M Hara 1, M Harigai 1, K Suzuki 1, Y Kawaguchi 1, T Ishizuka 1, M Kawagoe 1, H Nakamura 1
PMCID: PMC1554450  PMID: 1379131

Abstract

There is evidence to suggest that CD5+ B cells may be associated with autoimmunity, e.g. they are increased in patients with rheumatoid arthritis (RA). In this study, we found that the expression of CD5 on RA B cells increased spontaneously, following culture for up to 4 days in vitro in the absence of T cells, supporting the idea that the CD5+ B cell possesses distinctive features. The spontaneous increase of CD5 expression was down-regulated by recombinant IL-4 (rIL-4). Other cytokines studied (rIL-1 alpha, rIL-2, rIL-5, rIL-6) did not alter CD5 expression. Studies of antibody production showed that rIL-4 could reduce spontaneous production of total IgG and IgM in non-stimulated RA T plus B cell cultures. Spontaneous production of IgM rheumatoid factor (IgM-RF), measured by a newly developed avidin-biotin complex ELISA, was also reduced by rIL-4. Furthermore, rIL-4 reduced the increase in IgM-RF production observed on stimulation with Staphylococcus aureus Cowan I (SAC) or pokeweed mitogen (PWM). Thus, IL-4 might act as a regulator of the development of abnormal B cell differentiation in patients with RA.

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Selected References

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  1. Antin J. H., Emerson S. G., Martin P., Gadol N., Ault K. A. Leu-1+ (CD5+) B cells. A major lymphoid subpopulation in human fetal spleen: phenotypic and functional studies. J Immunol. 1986 Jan;136(2):505–510. [PubMed] [Google Scholar]
  2. Arnett F. C., Edworthy S. M., Bloch D. A., McShane D. J., Fries J. F., Cooper N. S., Healey L. A., Kaplan S. R., Liang M. H., Luthra H. S. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988 Mar;31(3):315–324. doi: 10.1002/art.1780310302. [DOI] [PubMed] [Google Scholar]
  3. Bofill M., Janossy G., Janossa M., Burford G. D., Seymour G. J., Wernet P., Kelemen E. Human B cell development. II. Subpopulations in the human fetus. J Immunol. 1985 Mar;134(3):1531–1538. [PubMed] [Google Scholar]
  4. Boumsell L., Coppin H., Pham D., Raynal B., Lemerle J., Dausset J., Bernard A. An antigen shared by a human T cell subset and B cell chronic lymphocytic leukemic cells. Distribution on normal and malignant lymphoid cells. J Exp Med. 1980 Jul 1;152(1):229–234. doi: 10.1084/jem.152.1.229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Casali P., Burastero S. E., Balow J. E., Notkins A. L. High-affinity antibodies to ssDNA are produced by CD-B cells in systemic lupus erythematosus patients. J Immunol. 1989 Dec 1;143(11):3476–3483. [PubMed] [Google Scholar]
  6. Casali P., Burastero S. E., Nakamura M., Inghirami G., Notkins A. L. Human lymphocytes making rheumatoid factor and antibody to ssDNA belong to Leu-1+ B-cell subset. Science. 1987 Apr 3;236(4797):77–81. doi: 10.1126/science.3105056. [DOI] [PubMed] [Google Scholar]
  7. Coffman R. L., Ohara J., Bond M. W., Carty J., Zlotnik A., Paul W. E. B cell stimulatory factor-1 enhances the IgE response of lipopolysaccharide-activated B cells. J Immunol. 1986 Jun 15;136(12):4538–4541. [PubMed] [Google Scholar]
  8. Dauphinée M., Tovar Z., Talal N. B cells expressing CD5 are increased in Sjögren's syndrome. Arthritis Rheum. 1988 May;31(5):642–647. doi: 10.1002/art.1780310509. [DOI] [PubMed] [Google Scholar]
  9. Defrance T., Aubry J. P., Rousset F., Vanbervliet B., Bonnefoy J. Y., Arai N., Takebe Y., Yokota T., Lee F., Arai K. Human recombinant interleukin 4 induces Fc epsilon receptors (CD23) on normal human B lymphocytes. J Exp Med. 1987 Jun 1;165(6):1459–1467. doi: 10.1084/jem.165.6.1459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. Defrance T., Vanbervliet B., Durand I., Banchereau J. Human interleukin 4 down-regulates the surface expression of CD5 on normal and leukemic B cells. Eur J Immunol. 1989 Feb;19(2):293–299. doi: 10.1002/eji.1830190212. [DOI] [PubMed] [Google Scholar]
  12. Defrance T., Vanbervliet B., Pène J., Banchereau J. Human recombinant IL-4 induces activated B lymphocytes to produce IgG and IgM. J Immunol. 1988 Sep 15;141(6):2000–2005. [PubMed] [Google Scholar]
  13. Freedman A. S., Freeman G., Whitman J., Segil J., Daley J., Levine H., Nadler L. M. Expression and regulation of CD5 on in vitro activated human B cells. Eur J Immunol. 1989 May;19(5):849–855. doi: 10.1002/eji.1830190511. [DOI] [PubMed] [Google Scholar]
  14. Hara M., Kitani A., Hirose T., Norioka K., Harigai M., Suzuki K., Tabata H., Kawakami M., Kawagoe M., Nakamura H. Stimulatory effect of CD5 antibody on B cells from patients with rheumatoid arthritis. Clin Immunol Immunopathol. 1988 Nov;49(2):223–230. doi: 10.1016/0090-1229(88)90112-2. [DOI] [PubMed] [Google Scholar]
  15. Hardy R. R., Hayakawa K., Shimizu M., Yamasaki K., Kishimoto T. Rheumatoid factor secretion from human Leu-1+ B cells. Science. 1987 Apr 3;236(4797):81–83. doi: 10.1126/science.3105057. [DOI] [PubMed] [Google Scholar]
  16. Hayakawa K., Hardy R. R., Herzenberg L. A., Herzenberg L. A. Progenitors for Ly-1 B cells are distinct from progenitors for other B cells. J Exp Med. 1985 Jun 1;161(6):1554–1568. doi: 10.1084/jem.161.6.1554. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hirano T., Taga T., Nakano N., Yasukawa K., Kashiwamura S., Shimizu K., Nakajima K., Pyun K. H., Kishimoto T. Purification to homogeneity and characterization of human B-cell differentiation factor (BCDF or BSFp-2). Proc Natl Acad Sci U S A. 1985 Aug;82(16):5490–5494. doi: 10.1073/pnas.82.16.5490. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hofman F. M., Brock M., Taylor C. R., Lyons B. IL-4 regulates differentiation and proliferation of human precursor B cells. J Immunol. 1988 Aug 15;141(4):1185–1190. [PubMed] [Google Scholar]
  19. Howard M., Farrar J., Hilfiker M., Johnson B., Takatsu K., Hamaoka T., Paul W. E. Identification of a T cell-derived b cell growth factor distinct from interleukin 2. J Exp Med. 1982 Mar 1;155(3):914–923. doi: 10.1084/jem.155.3.914. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Ishizaka A., Sakiyama Y., Nakanishi M., Tomizawa K., Oshika E., Kojima K., Taguchi Y., Kandil E., Matsumoto S. The inductive effect of interleukin-4 on IgG4 and IgE synthesis in human peripheral blood lymphocytes. Clin Exp Immunol. 1990 Mar;79(3):392–396. doi: 10.1111/j.1365-2249.1990.tb08101.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Iwatani Y., Amino N., Kaneda T., Ichihara K., Tamaki H., Tachi J., Matsuzuka F., Fukata S., Kuma K., Miyai K. Marked increase of CD5 + B cells in hyperthyroid Graves' disease. Clin Exp Immunol. 1989 Nov;78(2):196–200. [PMC free article] [PubMed] [Google Scholar]
  22. Jelinek D. F., Lipsky P. E. Inhibitory influence of IL-4 on human B cell responsiveness. J Immunol. 1988 Jul 1;141(1):164–173. [PubMed] [Google Scholar]
  23. Jyonouchi H., Voss R. M., Good R. A. Up-regulation and down-regulation of cell surface and mRNA expression of CD5 antigen by various humoral factors on murine 70Z/3 pre-B cell leukemia cell line: IL-4 down-regulates CD5 antigen expression. Cell Immunol. 1990 Oct 1;130(1):66–78. doi: 10.1016/0008-8749(90)90162-k. [DOI] [PubMed] [Google Scholar]
  24. Maeda M., Noma T., Hama K., Honjo T. Application of a human T cell line derived from a Sézary syndrome patient for human interleukin 4 assay. Immunol Lett. 1988 Aug;18(4):247–253. doi: 10.1016/0165-2478(88)90170-8. [DOI] [PubMed] [Google Scholar]
  25. Maeda M., Shimizu A., Ikuta K., Okamoto H., Kashihara M., Uchiyama T., Honjo T., Yodoi J. Origin of human T-lymphotrophic virus I-positive T cell lines in adult T cell leukemia. Analysis of T cell receptor gene rearrangement. J Exp Med. 1985 Dec 1;162(6):2169–2174. doi: 10.1084/jem.162.6.2169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Minamitake Y., Kodama S., Katayama T., Adachi H., Tanaka S., Tsujimoto M. Structure of recombinant human interleukin 5 produced by Chinese hamster ovary cells. J Biochem. 1990 Feb;107(2):292–297. doi: 10.1093/oxfordjournals.jbchem.a123041. [DOI] [PubMed] [Google Scholar]
  27. Mix E., Olsson T., Correale J., Baig S., Kostulas V., Olsson O., Link H. B cells expressing CD5 are increased in cerebrospinal fluid of patients with multiple sclerosis. Clin Exp Immunol. 1990 Jan;79(1):21–27. doi: 10.1111/j.1365-2249.1990.tb05121.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Mouritsen S. Rheumatoid factors are anti-idiotypic antibodies against virus-induced anti-Fc receptor antibodies. A hypothesis for the induction of some rheumatoid factors. Scand J Immunol. 1986 Nov;24(5):485–490. doi: 10.1111/j.1365-3083.1986.tb02162.x. [DOI] [PubMed] [Google Scholar]
  29. Nishida T., Nishino N., Takano M., Kawai K., Bando K., Masui Y., Nakai S., Hirai Y. cDNA cloning of IL-1 alpha and IL-1 beta from mRNA of U937 cell line. Biochem Biophys Res Commun. 1987 Feb 27;143(1):345–352. doi: 10.1016/0006-291x(87)90671-1. [DOI] [PubMed] [Google Scholar]
  30. Sanderson C. J. Eosinophil differentiation factor (interleukin-5). Immunol Ser. 1990;49:231–256. [PubMed] [Google Scholar]
  31. Sanderson C. J. The biological role of interleukin 5. Int J Cell Cloning. 1990 Jan;8 (Suppl 1):147–154. doi: 10.1002/stem.5530080713. [DOI] [PubMed] [Google Scholar]
  32. Snapper C. M., Finkelman F. D., Paul W. E. Differential regulation of IgG1 and IgE synthesis by interleukin 4. J Exp Med. 1988 Jan 1;167(1):183–196. doi: 10.1084/jem.167.1.183. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Snapper C. M., Paul W. E. B cell stimulatory factor-1 (interleukin 4) prepares resting murine B cells to secrete IgG1 upon subsequent stimulation with bacterial lipopolysaccharide. J Immunol. 1987 Jul 1;139(1):10–17. [PubMed] [Google Scholar]
  34. Spits H., Yssel H., Takebe Y., Arai N., Yokota T., Lee F., Arai K., Banchereau J., de Vries J. E. Recombinant interleukin 4 promotes the growth of human T cells. J Immunol. 1987 Aug 15;139(4):1142–1147. [PubMed] [Google Scholar]
  35. Splawski J. B., Jelinek D. F., Lipsky P. E. Immunomodulatory role of IL-4 on the secretion of Ig by human B cells. J Immunol. 1989 Mar 1;142(5):1569–1575. [PubMed] [Google Scholar]
  36. Suzuki N., Sakane T., Engleman E. G. Anti-DNA antibody production by CD5+ and CD5- B cells of patients with systemic lupus erythematosus. J Clin Invest. 1990 Jan;85(1):238–247. doi: 10.1172/JCI114418. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Tsujimoto M., Adachi H., Kodama S., Tsuruoka N., Yamada Y., Tanaka S., Mita S., Takatsu K. Purification and characterization of recombinant human interleukin 5 expressed in Chinese hamster ovary cells. J Biochem. 1989 Jul;106(1):23–28. doi: 10.1093/oxfordjournals.jbchem.a122812. [DOI] [PubMed] [Google Scholar]
  38. Werner-Favre C., Vischer T. L., Wohlwend D., Zubler R. H. Cell surface antigen CD5 is a marker for activated human B cells. Eur J Immunol. 1989 Jul;19(7):1209–1213. doi: 10.1002/eji.1830190709. [DOI] [PubMed] [Google Scholar]
  39. Wetzel G. D. Interleukin 5 regulation of peritoneal Ly-1 B lymphocyte proliferation, differentiation and autoantibody secretion. Eur J Immunol. 1989 Sep;19(9):1701–1707. doi: 10.1002/eji.1830190926. [DOI] [PubMed] [Google Scholar]

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