The Yaa gene-mediated acceleration of murine lupus: Yaa- T cells from non-autoimmune mice collaborate with Yaa+ B cells to produce lupus autoantibodies in vivo

Eur J Immunol. 1995 Dec;25(12):3412-7. doi: 10.1002/eji.1830251231.

Abstract

The BXSB Y chromosome-linked mutant gene, Yaa, promotes autoimmune responses in mice predisposed to a lupus-like autoimmune disease. We have previously shown that a cognate interaction of T cells with B cells expressing the Yaa gene appears to be responsible for the accelerated production of autoantibodies. To investigate whether T cells that provide help for autoantibody production by Yaa+ B cells need to express the Yaa gene, we have made radiation bone marrow chimeras containing two sets of T and B cells from mice with or without the Yaa gene and differing by the Thy-1 and Igh allotypes. We then determined autoantibody production following the selective elimination of T cells of Yaa+ origin by treating mice with allele-specific anti-Thy-1 monoclonal antibody. Our results demonstrated that the selective production of autoantibodies by Yaa+ B cells in Yaa(+)-Yaa- double bone marrow chimeras can be mediated as efficiently by T cells from non-autoimmune mice lacking the Yaa gene as by T cells from autoimmune mice bearing the Yaa gene. This indicates that T cells from non-autoimmune Yaa- mice are capable of providing help for autoimmune responses by collaborating with Yaa+ B cells. These data thus strongly suggest that the Yaa gene defect is not functionally expressed in T cells, but only in B cells, and contrast with parallel experiments in the lpr model, in which defects of the Fas antigen in both T and B cells are crucial for the lpr gene-mediated promotion of autoantibody production.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Autoantibodies / biosynthesis*
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Base Sequence
  • Bone Marrow / immunology
  • Female
  • Isoantibodies / pharmacology
  • Lupus Erythematosus, Systemic / etiology*
  • Lupus Erythematosus, Systemic / genetics*
  • Lymphocyte Cooperation / genetics*
  • Lymphocyte Depletion
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Molecular Sequence Data
  • Radiation Chimera
  • Syndrome
  • T-Lymphocytes / immunology*
  • Thy-1 Antigens / immunology
  • Y Chromosome / genetics*
  • Y Chromosome / immunology*

Substances

  • Autoantibodies
  • Isoantibodies
  • Thy-1 Antigens
  • anti-Thy antibody