Abstract
Binding and structural characteristics of human IgMk anti-ssDNA antibody 7B3 were determined. 7B3 was derived from Epstein-Barr virus-transformed peripheral blood B cells of a lupus nephritis patient. Purified 7B3 bound ssDNA from various species, but not dsDNA or structurally unrelated antigens. The relative avidity of 7B3 was high in comparison with IgM anti-DNA antibodies previously described by other investigators. Sequence analysis showed that 7B3 used VH26/D35/JH3 and Humkv328h5/JK1 germline genes, and had a few mutations in the complementarity determining regions (CDRs). No arginine was expressed in the heavy-chain CDR3. However, the putative DNA contact sites, based on the previous crystallographic and computer modeling studies, were occupied by mutated or germline-derived basic and polar amino acids. These results suggest that a minimally mutated IgM anti-ssDNA antibody with a paucity of arginines could display monospecificity and high avidity if DNA-binding amino acids are enriched at the critical DNA contact sites.
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