| Research Abstract |
The production of anti-DNA antibodies in SLE-prone NZB/W F1 mice show an age-associated IgM to IgG isotype-switching. A majority of IgM anti-DNA antibodies reported so far were shown to be germline-encoded, with no, if any, somatic mutation in the immunoglobulin variable (V) region. In contrast, IgG anti-DNA antibodies show somatic mutations in V regions, and B cells responsible for these antibody production are clonally selected and expanded. These findings suggest that while IgM anti-DNA antibodies are the product of antigen-nonspecific B cell activation, IgG anti-DNA antibodies are produced by antigen-specific mechanism.
In the present studies on examining IgM and IgG anti-DNA monoclonal antibodies derived from individual NZB/W F1 mice, we first demonstrate that IgM anti-DNA antibodies are also clonally selected and expanded and that somatic mutations in V regions are introduced before IgM to IgG isotype-switching. These somatic mutations are associated with the increase in DNA-binding activities, suggesting that, in contrast to the previous speculation, IgM anti-DNA antibodies are also produced by antigen-specific mechanism as in the case of IgG anti-DNA antibodies.
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