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The Journal of Immunology, Vol 154, Issue 9 4444-4455, Copyright © 1995 by American Association of Immunologists

ARTICLES

B cell selection and allelic exclusion of an anti-DNA Ig transgene in MRL-lpr/lpr mice

JH Roark, CL Kuntz, KA Nguyen, L Mandik, M Cattermole and J Erikson
Wistar Institute, Philadelphia, PA 19104, USA.

We have used an Ig transgene (VH3H9) that increases the frequency of anti-DNA autoantibodies to address whether the production of antinuclear Abs in systemic lupus erythematosus is the consequence of a breakdown of B cell tolerance. We have shown that nonautoimmune mice regulate anti-DNA B cells, and that lupus-prone MRL-lpr/lpr mice are defective in this regulation. Here we show that a subset of anti-DNA B cells, namely those that stain nuclei in a homogeneous fashion, not only fail to be deleted in MRL-lpr/lpr mice, but undergo preferential clonal expansion. In addition, we describe a surprising finding: the VH3H9 transgene is less efficient at inhibiting endogenous heavy chain gene rearrangement on the autoimmune-prone MRL-lpr/lpr genetic background than on the nonautoimmune BALB/c background.


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