Expression of anti-DNA immunoglobulin transgenes in non-autoimmune mice

J Erikson, MZ Radic, SA Camper, RR Hardy… - Nature, 1991 - nature.com
J Erikson, MZ Radic, SA Camper, RR Hardy, C Carmack, M Weigert
Nature, 1991nature.com
Abstract SELF-REACTIVE B cells can be regulated by either deletion or inactivation1. These
manifestations of self-tolerance have been dramatically shown in transgenic mice in which
the number of self-reactive cells has been artificially expanded2, 3. We have now extended
these models to ask if B-cell tolerance as described for non-disease-associated antigens
also operates for the targets of autoimmunity. The target we have chosen is DNA. Anti-DNA
antibodies are diagnostic of certain autoimmune syndromes in humans and are a …
Abstract
SELF-REACTIVE B cells can be regulated by either deletion or inactivation1. These manifestations of self-tolerance have been dramatically shown in transgenic mice in which the number of self-reactive cells has been artificially expanded2,3. We have now extended these models to ask if B-cell tolerance as described for non-disease-associated antigens also operates for the targets of autoimmunity. The target we have chosen is DNA. Anti-DNA antibodies are diagnostic of certain autoimmune syndromes in humans and are a characteristic of the murine model of systemic autoimmunity, the MRI/ipr mouse4. Antibodies to both single-stranded and double-stranded DNA have been implicated in disease5,6. By generating anti-DNA transgenic mice, we have addressed the question of whether DNA-specific B cells are regulated in normal (non-autoimmune) mice. We indeed found that most transgenic B cells bind DNA, yet we failed to detect secreted anti-DNA. We suggest that as a consequence of their self-reactivity these B cells are developmentally arrested.
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