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.
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.
Fossati
L
L
Department of Pathology, University of Geneva, Switzerland.
Sobel
E S
ES
Iwamoto
M
M
Cohen
P L
PL
Eisenberg
R A
RA
Izui
S
S
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D001483:Base Sequence; D001853:Bone Marrow / Q000276:immunology; D005260:Female; D007518:Isoantibodies / Q000494:pharmacology; D008180:Lupus Erythematosus, Systemic / Q000209:etiology* / Q000235:genetics*; D008211:Lymphocyte Cooperation / Q000235:genetics*; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D011828:Radiation Chimera; D013577:Syndrome; D013601:T-Lymphocytes / Q000276:immunology*; D018800:Thy-1 Antigens / Q000276:immunology; D014998:Y Chromosome / Q000235:genetics* / Q000276:immunology*
D001323:Autoantibodies; D007518:Isoantibodies; D018800:Thy-1 Antigens; C035678:anti-Thy antibody