Efficient peripheral clonal elimination of B lymphocytes in MRL/lpr mice bearing autoantibody transgenes.
Peripheral B cell tolerance was studied in mice of the autoimmune-prone, Fas-deficient MRL/ lpr.H-2(d) genetic background by introducing a transgene that directs expression of membrane-bound H-2Kb antigen to liver and kidney (MT-Kb) and a second transgene encoding antibody reactive with this antigen (3-83mu delta, anti-Kk,b). Control immunoglobulin transgenic (Ig-Tg) MRL/lpr.H-2(d) mice lacking the Kb antigen had large numbers of splenic and lymph node B cells bearing the transgene-encoded specificity, whereas B cells of the double transgenic (Dbl-Tg) MRL/lpr.H-2(d) mice were deleted as efficiently as in Dbl-Tg mice of a nonautoimmune B10.D2 genetic background. In spite of the severely restricted peripheral B cell repertoire of the Ig-Tg MRL/lpr.H-2(d) mice, and notwithstanding deletion of the autospecific B cell population in the Dbl-Tg MRL/lpr.H-2(d) mice, both types of mice developed lymphoproliferation and exhibited elevated levels of IgG anti-chromatin autoantibodies. Interestingly, Dbl-Tg MRL/lpr.H-2(d) mice had a shorter lifespan than Ig-Tg MRL/lpr.H-2(d) mice, apparently as an indirect result of their relative B cell lymphopenia. These data suggest that in MRL/lpr mice peripheral B cell tolerance is not globally defective, but that certain B cells with receptors specific for nuclear antigens are regulated differently than are cells reactive to membrane autoantigens.
Kench
J A
JA
National Jewish Medical and Research Center, Division of Basic Sciences, Department of Pediatrics, Denver, Colorado 80206, USA.
Russell
D M
DM
Nemazee
D
D
D000375:Aging / Q000235:genetics / Q000276:immunology; D000818:Animals; D001323:Autoantibodies / Q000097:blood / Q000235:genetics*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D017637:Clonal Deletion; D006183:H-2 Antigens / Q000235:genetics; D006965:Hyperplasia; D007106:Immune Sera / Q000235:genetics; D008198:Lymph Nodes / Q000473:pathology; D008232:Lymphoproliferative Disorders / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr / Q000235:genetics* / Q000276:immunology; D008822:Mice, Transgenic; D019076:Transgenes / Q000276:immunology*
D001323:Autoantibodies; D006183:H-2 Antigens; D007106:Immune Sera