Analysis of anti-DNA antibodies derived from BALB/c mice

Abstract

I have generated a panel of four anti-DNA antibodies which express a member of the S107 V{dollar}\sb{lcub}\rm H{rcub}{dollar} gene family from BALB/c mice. The S107 family encodes for antibodies which are protective against pneumococcal bacteria infection and also encodes for antibodies which bind to influenza virus. Previous studies have shown that a single nucleotide substitution in an S107 V{dollar}\sb{lcub}\rm H{rcub}{dollar} region can change the specificity of a protective anti-phosphorylcholine antibody to an anti-double-stranded (ds) DNA antibody. Recent analyses have also shown that anti-dsDNA antibodies derived from autoimmune mice can express a member of the S107 V{dollar}\sb{lcub}\rm H{rcub}{dollar} family. The antibodies I have isolated display many characteristics associated with the pathogenic antibodies that have been derived from autoimmune animals, except that they are not somatically mutated. The combined characteristics of these antibodies identify them as a novel class of anti-DNA antibodies not before seen in autoimmune or nonautoimmune animals. Their isolation in nonautoimmune BALB/c mice stimulates important questions regarding the regulation of autoantibodies in autoimmunity and in the normal immune response.;In the course of analyzing these antibodies, I have identified a new V{dollar}\sb\kappa{dollar} gene family. This family is highly expressed in an autoimmune mouse strain. The analysis of this gene family has led to the consideration of issues regarding the preferential expression of particular V gene families in autoimmune disease. Finally, I have made the observation that isotype switch variants of the anti-DNA antibodies that I have analyzed may bind better to DNA attached to a solid phase. This observation has led to the consideration of issues regarding the assessment of pathogenicity of anti-DNA antibodies.