J. Exp. Med., Volume 188, Number 5, September 7, 1998 909-917

Efficient Peripheral Clonal Elimination of B Lymphocytes in MRL/lpr Mice Bearing Autoantibody Transgenes

By Jennifer A. Kench,^* David M. Russell,^* and David Nemazee^*

From the ^* National Jewish Medical and Research Center, Division of Basic Sciences, Department of Pediatrics, Denver, Colorado 80206; and the  Department of Immunology, University of Colorado Health Sciences Center, Denver, Colorado 80206

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-2K^b antigen to liver and kidney (MT-K^b) and a second transgene encoding antibody reactive with this antigen (3-83µ, anti-K^k,b). Control immunoglobulin transgenic (Ig-Tg) MRL/lpr.H-2^d mice lacking the K^b 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.

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