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Related Experiment Videos

T cell autoimmunity in Ig transgenic mice.

S Shinde1, R Gee, S Santulli-Marotto

  • 1Section of Rheumatology, Yale University School of Medicine, New Haven, CT 06520, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|June 8, 1999
PubMed
Summary

Autoimmune B cells specific for U1/Sm ribonucleoprotein (snRNP) can activate autoreactive T cells in systemic lupus erythematosus models. These findings highlight the role of autoreactive B lymphocytes in T cell activation.

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Area of Science:

  • Immunology
  • Autoimmunity
  • Molecular Biology

Background:

  • Autoantibodies against U1/Sm ribonucleoprotein (snRNP) are hallmarks of systemic lupus erythematosus (SLE).
  • The MRL murine model exhibits these characteristic autoantibodies, making it a relevant model for SLE research.

Purpose of the Study:

  • To investigate the function of transgenic B lymphocytes in regulating autoreactive T cells against the snRNP autoantigen.
  • To understand the mechanisms underlying T cell activation in the context of autoimmunity.

Main Methods:

  • Development of transgenic mice expressing an Ig heavy chain specific for the D protein of murine snRNP.
  • Analysis of B lymphocyte phenotype (immature, heat-stable Ag high).
  • Examination of T lymphocyte responses using recombinant snRNP D protein and antigen-presenting cells (APCs).

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Main Results:

  • Transgenic anti-snRNP B cell APCs effectively stimulated CD4 T cells from wild-type C57BL/6 and MRL lpr/lpr mice.
  • Non-specific APCs failed to elicit a similar T cell response, indicating the importance of antigen specificity.
  • snRNP-reactive T cells in C57BL/6 transgenic mice showed tolerance, unlike those in MRL lpr/lpr transgenic mice.

Conclusions:

  • Autoreactive T cells are present but not deleted in wild-type mice, with activation facilitated by autoantigen-specific APCs.
  • Autoreactive B lymphocytes play a significant role in the in vivo activation and/or diversification of autoreactive T cells.
  • Differences in tolerance induction between C57BL/6 and MRL lpr/lpr transgenic mice suggest distinct regulatory pathways in autoimmunity.