Ionic Binding Characteristics of Monoclonal Autoantibodies to DNA from NZB.H-2^bm12 Mice

Abstract

NZB (H-2^d) mice are well known for the production of IgM autoantibodies to ssDNA. However, an FI cross between NZB and either NZW or SWR mice is required to produce IgG nephritogenic antibodies to dsDNA and glomerulonephritis. The contribution of parental class II loci in the hybrid mice is clearly important to the development of anti-dsDNA antibodies, In contrast, NZB mice congenic with the la^bm12 mutation develop IgG autoantibodies to dsDNA despite being homozygous for Ia. As a part of our effort to examine the mechanisms of disease development in NZB.H-2^bm12 mice, we have generated a panel of monoclonal antibodies against nucleic acids. A subgroup of these antibodies exhibited strong electrostatic interaction with nucleic acids as evidenced by inhibition of their binding by a moderate increase in ionic strength. Interestingly, the effect of salt was either all or none; e.g., antibodies were either markedly inhibited or virtually unaffected. The importance of this ionic interaction was highlighted by analysis of DNA binding of antibodies from serum and nephritic kidneys of NZB.H-2^bm12 mice. Antibodies specific for ssDNA, which are common in NZB mice and not associated with nephritic lupus, are largely unaffected by salt. However, serum and kidney eluted IgG antibodies specific for dsDNA were markedly inhibited by salt. We postulate that B cell clones whose antibodies exhibit electrostatic interaction with DNA are preferentially expanded during the course of lupus in NZB.H-2^bm12 mice and that such antibodies contribute significantly to glomerulonephritis.

Key Words:

• New Zealand mice
• antibodies to dsDNA
• Ia^bm12
• hybridomas