Skip to main content
Immunology logoLink to Immunology
. 1987 Jul;61(3):369–374.

Origin of the autoreactive anti-type II collagen response. I. Frequency of specific and multispecific B cells in primed murine lymph nodes.

R Holmdahl, M Andersson, A Tarkowski
PMCID: PMC1453413  PMID: 2440798

Abstract

DBA/1 mice develop systemic polyarthritis and high titres of collagen autoantibodies after immunization with type II collagen. In this study we have analysed the frequency and specificity of antibody-producing B cells in draining lymph nodes 11 days after a primary immunization with rat type II collagen. A remarkably high frequency of type II collagen-reactive hybridomas (30%, n = 71), the majority cross-reacting with autologous type II collagen, were generated. Most of the collagen-reactive hybridomas produced IgG antibodies specific for type II collagen. Many other hybridomas produced multispecific antibodies (9%): these were preferentially of the IgM class. Some of the monoclonal multispecific hybridomas produced antibodies that cross-reacted with specific epitopes on the collagen molecule. One type II collagen-reactive hybridoma also displayed rheumatoid factor activity. Different mechanisms for the generation of the high frequency of collagen reactive antibodies are discussed.

Full text

PDF

Selected References

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

  1. De Blas A. L., Ratnaparkhi M. V., Mosimann J. E. Estimation of the number of monoclonal hybridomas in a cell fusion experiment. Effect of post-fusion cell dilution on hybridoma survival. J Immunol Methods. 1981;45(2):109–115. doi: 10.1016/0022-1759(81)90205-2. [DOI] [PubMed] [Google Scholar]
  2. Dighiero G., Lymberi P., Mazié J. C., Rouyre S., Butler-Browne G. S., Whalen R. G., Avrameas S. Murine hybridomas secreting natural monoclonal antibodies reacting with self antigens. J Immunol. 1983 Nov;131(5):2267–2272. [PubMed] [Google Scholar]
  3. Holmberg D., Forsgren S., Ivars F., Coutinho A. Reactions among IgM antibodies derived from normal, neonatal mice. Eur J Immunol. 1984 May;14(5):435–441. doi: 10.1002/eji.1830140510. [DOI] [PubMed] [Google Scholar]
  4. Holmdahl R., Jansson L., Gullberg D., Rubin K., Forsberg P. O., Klareskog L. Incidence of arthritis and autoreactivity of anti-collagen antibodies after immunization of DBA/1 mice with heterologous and autologous collagen II. Clin Exp Immunol. 1985 Dec;62(3):639–646. [PMC free article] [PubMed] [Google Scholar]
  5. Holmdahl R., Klareskog L., Rubin K., Björk J., Smedegård G., Jonsson R., Andersson M. Role of T lymphocytes in murine collagen induced arthritis. Agents Actions. 1986 Dec;19(5-6):295–305. doi: 10.1007/BF01971231. [DOI] [PubMed] [Google Scholar]
  6. Holmdahl R., Klareskog L., Rubin K., Larsson E., Wigzell H. T lymphocytes in collagen II-induced arthritis in mice. Characterization of arthritogenic collagen II-specific T-cell lines and clones. Scand J Immunol. 1985 Sep;22(3):295–306. doi: 10.1111/j.1365-3083.1985.tb01884.x. [DOI] [PubMed] [Google Scholar]
  7. Holmdahl R., Moran T., Andersson M. A rapid and efficient immunization protocol for production of monoclonal antibodies reactive with autoantigens. J Immunol Methods. 1985 Nov 7;83(2):379–384. doi: 10.1016/0022-1759(85)90260-1. [DOI] [PubMed] [Google Scholar]
  8. Holmdahl R., Rubin K., Klareskog L., Larsson E., Wigzell H. Characterization of the antibody response in mice with type II collagen-induced arthritis, using monoclonal anti-type II collagen antibodies. Arthritis Rheum. 1986 Mar;29(3):400–410. doi: 10.1002/art.1780290314. [DOI] [PubMed] [Google Scholar]
  9. Jerne N. K. THE NATURAL-SELECTION THEORY OF ANTIBODY FORMATION. Proc Natl Acad Sci U S A. 1955 Nov 15;41(11):849–857. doi: 10.1073/pnas.41.11.849. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Klareskog L., Holmdahl R., Larsson E., Wigzell H. Role of T lymphocytes in collagen II induced arthritis in rats. Clin Exp Immunol. 1983 Jan;51(1):117–125. [PMC free article] [PubMed] [Google Scholar]
  11. Köhler G., Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975 Aug 7;256(5517):495–497. doi: 10.1038/256495a0. [DOI] [PubMed] [Google Scholar]
  12. MacLennan I. C., Gray D. Antigen-driven selection of virgin and memory B cells. Immunol Rev. 1986 Jun;91:61–85. doi: 10.1111/j.1600-065x.1986.tb01484.x. [DOI] [PubMed] [Google Scholar]
  13. Miller E. J. Structural studies on cartilage collagen employing limited cleavage and solubilization with pepsin. Biochemistry. 1972 Dec 19;11(26):4903–4909. doi: 10.1021/bi00776a005. [DOI] [PubMed] [Google Scholar]
  14. Shlomchik M. J., Nemazee D. A., Sato V. L., Van Snick J., Carson D. A., Weigert M. G. Variable region sequences of murine IgM anti-IgG monoclonal autoantibodies (rheumatoid factors). A structural explanation for the high frequency of IgM anti-IgG B cells. J Exp Med. 1986 Aug 1;164(2):407–427. doi: 10.1084/jem.164.2.407. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Stuart J. M., Dixon F. J. Serum transfer of collagen-induced arthritis in mice. J Exp Med. 1983 Aug 1;158(2):378–392. doi: 10.1084/jem.158.2.378. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Trentham D. E., Townes A. S., Kang A. H. Autoimmunity to type II collagen an experimental model of arthritis. J Exp Med. 1977 Sep 1;146(3):857–868. doi: 10.1084/jem.146.3.857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Ware C. F., Reade J. L., Der L. C. A rat anti-mouse kappa chain specific monoclonal antibody, 187.1.10: purification, immunochemical properties and its utility as a general second-antibody reagent. J Immunol Methods. 1984 Nov 16;74(1):93–104. doi: 10.1016/0022-1759(84)90371-5. [DOI] [PubMed] [Google Scholar]
  18. Wolf B., Bashey R. I., Newton C. D., Jimenez S. A. Development of rheumatoid factors and anti-F(ab')2 antibodies in guinea pigs immunized with type II bovine collagen. Int Arch Allergy Appl Immunol. 1986;80(2):214–220. doi: 10.1159/000234054. [DOI] [PubMed] [Google Scholar]
  19. Wooley P. H., Luthra H. S., Stuart J. M., David C. S. Type II collagen-induced arthritis in mice. I. Major histocompatibility complex (I region) linkage and antibody correlates. J Exp Med. 1981 Sep 1;154(3):688–700. doi: 10.1084/jem.154.3.688. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES