T cell autoimmunity in Ig transgenic mice.
Autoantibodies directed at a diverse group of proteins of the U1/Sm ribonucleoprotein (snRNP) are characteristic of systemic lupus erythematosus and are found in the MRL murine model of this disease. This study examines the role of transgenic B lymphocytes in the regulation of autoreactive T cells to the snRNP autoantigen. Transgenic mice were developed bearing an Ig heavy chain gene specific for the D protein component of murine snRNP. B lymphocytes in these mice are neither deleted nor anergic and are of an immature (heat-stable Aghigh) phenotype. T lymphocytes from anti-snRNP transgenic mice were examined using a recombinant form of the D protein of the murine snRNP complex. Our results revealed that transgenic anti-snRNP B cell APCs stimulated CD4 T cells from wild-type C57BL/6 and MRL lpr/lpr mice, while nonspecific APCs failed to stimulate CD4 T cells. This study demonstrates that autoreactive T cells are not deleted from wild-type mice, although their activation is facilitated by autoantigen-specific APCs. The snRNP-reactive T cells in C57BL/6 transgenic mice are tolerized, in contrast to those T cells from MRL lpr/lpr transgenic mice. These studies implicate a role for autoreactive B lymphocytes in the in vivo activation and/or diversification of autoreactive T cells.
Shinde
S
S
Section of Rheumatology, Yale University School of Medicine, New Haven, CT 06520, USA.
Gee
R
R
Santulli-Marotto
S
S
Bockenstedt
L K
LK
Clarke
S H
SH
Mamula
M J
MJ
D000818:Animals; D017951:Antigen Presentation; D001324:Autoantigens / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D005803:Genes, Immunoglobulin / Q000235:genetics*; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D008822:Mice, Transgenic; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D017411:Ribonucleoproteins, Small Nuclear / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D001324:Autoantigens; D000949:Histocompatibility Antigens Class II; D010455:Peptides; D011947:Receptors, Antigen, B-Cell; D017411:Ribonucleoproteins, Small Nuclear