Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1988 Dec 1;168(6):1979–1992. doi: 10.1084/jem.168.6.1979

Monoreactive high affinity and polyreactive low affinity rheumatoid factors are produced by CD5+ B cells from patients with rheumatoid arthritis

PMCID: PMC2189135  PMID: 3264319

Abstract

In patients with rheumatoid arthritis (RA), circulating CD5+ B lymphocytes, but not CD5- B lymphocytes, are increased in number and size, exist in an activated state, spontaneously proliferate, and secrete Ig that binds to the Fc fragment of IgG. By constructing continuous mAb-secreting cell lines from CD5+ B lymphocytes, the properties and dissociation constants (Kd) of these antibodies were determined. Two types of rheumatoid factors (RFs) with discrete reactivities were produced. The first type is polyreactive and binds with relatively low affinity (Kd, 10(-5) mol/liter) to the Fc fragment of IgG. These antibodies are similar to those produced by CD5+ B cells from healthy subjects. The second type of RF is monoreactive and binds with higher affinity (Kd, 10(-7) mol/liter) to the Fc fragment of IgG. These latter autoantibodies are produced by CD5+ B cells of RA patients, but not healthy subjects. Long-term longitudinal studies are needed to determine the role of these two types of RFs in the pathogenesis of RA.

Full Text

The Full Text of this article is available as a PDF (1.0 MB).

Selected References

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

  1. Boling E. P., Ohishi T., Wahl S. M., Misiti J., Wistar R., Jr, Wilder R. L. Humoral immune function in severe, active rheumatoid arthritis. Clin Immunol Immunopathol. 1987 May;43(2):185–194. doi: 10.1016/0090-1229(87)90126-7. [DOI] [PubMed] [Google Scholar]
  2. Caligaris-Cappio F., Gobbi M., Bofill M., Janossy G. Infrequent normal B lymphocytes express features of B-chronic lymphocytic leukemia. J Exp Med. 1982 Feb 1;155(2):623–628. doi: 10.1084/jem.155.2.623. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Carson D. A., Bayer A. S., Eisenberg R. A., Lawrance S., Theofilopoulos A. IgG rheumatoid factor in subacute bacterial endocarditis: relationship to IgM rheumatoid factor and circulating immune complexes. Clin Exp Immunol. 1978 Jan;31(1):100–103. [PMC free article] [PubMed] [Google Scholar]
  4. Carson D. A., Chen P. P., Fox R. I., Kipps T. J., Jirik F., Goldfien R. D., Silverman G., Radoux V., Fong S. Rheumatoid factor and immune networks. Annu Rev Immunol. 1987;5:109–126. doi: 10.1146/annurev.iy.05.040187.000545. [DOI] [PubMed] [Google Scholar]
  5. Casali P., Inghirami G., Nakamura M., Davies T. F., Notkins A. L. Human monoclonals from antigen-specific selection of B lymphocytes and transformation by EBV. Science. 1986 Oct 24;234(4775):476–479. doi: 10.1126/science.3020687. [DOI] [PubMed] [Google Scholar]
  6. Casali P., Prabhakar B. S., Notkins A. L. Characterization of multireactive autoantibodies and identification of Leu-1+ B lymphocytes as cells making antibodies binding multiple self and exogenous molecules. Int Rev Immunol. 1988 Mar;3(1-2):17–45. doi: 10.3109/08830188809051180. [DOI] [PubMed] [Google Scholar]
  7. Engleman E. G., Warnke R., Fox R. I., Dilley J., Benike C. J., Levy R. Studies of a human T lymphocyte antigen recognized by a monoclonal antibody. Proc Natl Acad Sci U S A. 1981 Mar;78(3):1791–1795. doi: 10.1073/pnas.78.3.1791. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fox R., Sportsman R., Rhodes G., Luka J., Pearson G., Vaughan J. Rheumatoid arthritis synovial membrane contains a 62,000-molecular-weight protein that shares an antigenic epitope with the Epstein-Barr virus-encoded associated nuclear antigen. J Clin Invest. 1986 May;77(5):1539–1547. doi: 10.1172/JCI112469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Friguet B., Chaffotte A. F., Djavadi-Ohaniance L., Goldberg M. E. Measurements of the true affinity constant in solution of antigen-antibody complexes by enzyme-linked immunosorbent assay. J Immunol Methods. 1985 Mar 18;77(2):305–319. doi: 10.1016/0022-1759(85)90044-4. [DOI] [PubMed] [Google Scholar]
  10. Hayakawa K., Hardy R. R., Honda M., Herzenberg L. A., Steinberg A. D., Herzenberg L. A. Ly-1 B cells: functionally distinct lymphocytes that secrete IgM autoantibodies. Proc Natl Acad Sci U S A. 1984 Apr;81(8):2494–2498. doi: 10.1073/pnas.81.8.2494. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Inghirami G., Nakamura M., Balow J. E., Notkins A. L., Casali P. Model for studying virus attachment: identification and quantitation of Epstein-Barr virus-binding cells by using biotinylated virus in flow cytometry. J Virol. 1988 Jul;62(7):2453–2463. doi: 10.1128/jvi.62.7.2453-2463.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kipps T. J., Vaughan J. H. Genetic influence on the levels of circulating CD5 B lymphocytes. J Immunol. 1987 Aug 15;139(4):1060–1064. [PubMed] [Google Scholar]
  13. Klinman D. M., Steinberg A. D. Systemic autoimmune disease arises from polyclonal B cell activation. J Exp Med. 1987 Jun 1;165(6):1755–1760. doi: 10.1084/jem.165.6.1755. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Nakamura M., Burastero S. E., Notkins A. L., Casal P. Human monoclonal rheumatoid factor-like antibodies from CD5 (Leu-1)+ B cells are polyreactive. J Immunol. 1988 Jun 15;140(12):4180–4186. [PubMed] [Google Scholar]
  15. Otten G. R., Loken M. R. Two color light scattering identifies physical differences between lymphocyte subpopulations. Cytometry. 1982 Nov;3(3):182–187. doi: 10.1002/cyto.990030308. [DOI] [PubMed] [Google Scholar]
  16. Painter C. J., Monestier M., Chew A., Bona-Dimitriu A., Kasturi K., Bailey C., Scott V. E., Sidman C. L., Bona C. A. Specificities and V genes encoding monoclonal autoantibodies from viable motheaten mice. J Exp Med. 1988 Mar 1;167(3):1137–1153. doi: 10.1084/jem.167.3.1137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Plater-Zyberk C., Maini R. N., Lam K., Kennedy T. D., Janossy G. A rheumatoid arthritis B cell subset expresses a phenotype similar to that in chronic lymphocytic leukemia. Arthritis Rheum. 1985 Sep;28(9):971–976. doi: 10.1002/art.1780280903. [DOI] [PubMed] [Google Scholar]
  18. Portnoï D., Freitas A., Holmberg D., Bandeira A., Coutinho A. Immunocompetent autoreactive B lymphocytes are activated cycling cells in normal mice. J Exp Med. 1986 Jul 1;164(1):25–35. doi: 10.1084/jem.164.1.25. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. ROPES M. W., BENNETT G. A., COBB S., JACOX R., JESSAR R. A. 1958 Revision of diagnostic criteria for rheumatoid arthritis. Bull Rheum Dis. 1958 Dec;9(4):175–176. [PubMed] [Google Scholar]
  20. Radoux V., Chen P. P., Sorge J. A., Carson D. A. A conserved human germline V kappa gene directly encodes rheumatoid factor light chains. J Exp Med. 1986 Dec 1;164(6):2119–2124. doi: 10.1084/jem.164.6.2119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Shlomchik M. J., Aucoin A. H., Pisetsky D. S., Weigert M. G. Structure and function of anti-DNA autoantibodies derived from a single autoimmune mouse. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9150–9154. doi: 10.1073/pnas.84.24.9150. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Shlomchik M. J., Marshak-Rothstein A., Wolfowicz C. B., Rothstein T. L., Weigert M. G. The role of clonal selection and somatic mutation in autoimmunity. 1987 Aug 27-Sep 2Nature. 328(6133):805–811. doi: 10.1038/328805a0. [DOI] [PubMed] [Google Scholar]
  23. Taniguchi O., Miyajima H., Hirano T., Noguchi M., Ueda A., Hashimoto H., Hirose S., Okumura K. The Leu-1 B-cell subpopulation in patients with rheumatoid arthritis. J Clin Immunol. 1987 Nov;7(6):441–448. doi: 10.1007/BF00915053. [DOI] [PubMed] [Google Scholar]
  24. Ternynck T., Avrameas S. Murine natural monoclonal autoantibodies: a study of their polyspecificities and their affinities. Immunol Rev. 1986 Dec;94:99–112. doi: 10.1111/j.1600-065x.1986.tb01166.x. [DOI] [PubMed] [Google Scholar]
  25. Theofilopoulos A. N., Dixon F. J. Murine models of systemic lupus erythematosus. Adv Immunol. 1985;37:269–390. doi: 10.1016/s0065-2776(08)60342-9. [DOI] [PubMed] [Google Scholar]
  26. Welch M. J., Fong S., Vaughan J., Carson D. Increased frequency of rheumatoid factor precursor B lymphocytes after immunization of normal adults with tetanus toxoid. Clin Exp Immunol. 1983 Feb;51(2):299–304. [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES