<原著>抗DNA抗体遺伝子の突然変異, クラス転換と抗原親和性の変化

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Autoimmune-prone NZB×NZWF1 (NZB/WF1) mice produce IgM anti-DNA antibodies in early life. However, at about 5-6 months of age IgG anti-DNA antibodies begin to develop and the titer exceeds that of IgM anti-DNA antibodies. To investigate the changes in V_H gene and affinity maturation associated with isotype-switching in such anti-DNA antibodies, we established several monoclonal anti-DNA antibodies of both IgM and IgG classes from one NZB/WF1 mouse and sequenced the V_H, D and J_H regions of the immunoglobulin heavy chain gene. Among them, one pair of IgM and IgG monoclonal antibodies was suggested to use the same ancestor V_H genes in the Q52 family. The V_H segment sequence of the IgM anti-DNA antibody clone was identical to that of a cloned NZW germline V_H gene except for the priming sites. Thus it was probably encoded by unmutated germline V_H genes. By contrast, the V_H segment of the IgG counterpart contained many somatically mutated sequences. The IgG anti-DNA antibody showed a higher DNA-binding activity than did the IgM antibody. This may be the first direct demonstration that the germline-encoded, low affinity IgM autoantibody could undergo somatic mutations associated with isotype-switching by an antigen-driven mechanism, which resulted in the acquisition of high affinity, as seen in normal immune responses. Such a mechanism may be responsible for the generation of pathogenic autoantibodies in autoimmune diseases.
近畿大学の論文
1991-12-25

<原著>抗DNA抗体遺伝子の突然変異, クラス転換と抗原親和性の変化

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