Origin of class-specific anti-DNA antibodies

SLE易感NZB/W F1小鼠中抗DNA抗体的产生显示出与年龄相关的IgM至IgG同种型转换。迄今为止报道的大多数IgM抗DNA抗体被证明是种系编码的，在免疫球蛋白可变（V）区没有（如果有的话）体细胞突变。相反，IgG抗DNA抗体在V区显示体细胞突变，并且克隆选择和扩增负责这些抗体产生的B细胞。这些结果表明，IgM抗DNA抗体是抗原非特异性B细胞活化的产物，而IgG抗DNA抗体是通过抗原特异性机制产生的。我们首先证明了IgM抗-DNA抗体也被克隆选择和扩增，并且在IgM到IgG同种型转换之前引入V区中的体细胞突变。这些体细胞突变与DNA结合活性的增加有关，这表明，与先前的推测相反，IgM抗DNA抗体也是通过抗原特异性机制产生的，如IgG抗DNA抗体的情况。

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.