STRUCTURE AND ONTOGENY OF AUTOIMMUNE ANTI-DNA ANTIBODIES

自身免疫性疾病系统性狼疮的一个特征 红斑是DNA抗体的出现。 这也是 对于狼疮实验模型（NZB x NZW）F1小鼠来说，这是真的。 抗DNA抗体可以在小鼠和人类中诱导， 非特异性多克隆B细胞活化剂。 但只有 自身免疫性小鼠和狼疮患者产生持续的 抗DNA抗体反应。 此外，只有自身免疫小鼠和 狼疮患者产生IgG抗DNA抗体。 虽然IgM 自身免疫小鼠中的抗DNA抗体具有以下特征： 非特异性诱导的多克隆抗体群， 最近的证据表明，IgG抗DNA抗体可能是 克隆限制。 本文概述的实验设计 分析IgM和IgG抗DNA的克隆多样性 自身免疫（NZB x NZw）F1小鼠中的抗体。 他们也是 旨在确定IgG抗DNA抗体是否与 早期出现的IgM抗DNA抗体， 个体自身免疫小鼠。 此外，这些实验将 确定IgG抗DNA抗体产生B细胞是否 从较早出现的IgM抗DNA抗体中克隆选择- 产生B细胞。 这些实验将决定 DNA结合的变化伴随着IgM到IgG的转换， DNA抗体 最后，这些实验将确定 免疫球蛋白可变区基因体细胞突变伴随 同种型转换 希望这些实验的结果 将提供新的洞察力的过程，运作， 在自身免疫小鼠和人类中产生DNA抗体， 狼疮

A characteristic of the autoimmune disease systemic lupus erythematosus is the appearance of antibodies to DNA. This is also true for (NZB x NZW) F1 mice, an experimental model for lupus. Anti-DNA antibodies can be induced in both mice and humans with non-specific polyclonal B cell activators. However, only autoimmune mice and individuals with lupus generate a sustained anti-DNA antibody response. Moreover, only autoimmune mice and humans with lupus produce IgG anti-DNA antibodies. Although IgM anti-DNA antibodies in autoimmune mice have the characteristics of a non-specifically induced, polyclonal population of antibodies, recent evidence suggests that the IgG anti-DNA antibodies may be clonally restricted. The experiments outline herein are designed to analyze the clonal diversity of both IgM and IgG anti-DNA antibodies in autoimmune (NZB x NZw) F1 mice. They are also designed to determine whether IgG anti-DNA antibodies are related to the earlier appearing IgM anti-DNA antibodies within an individual autoimmune mouse. Moreover, these experiments will determine whether IgG anti-DNA antibody-producing B cells are clonally selected from earlier appearing IgM anti-DNA antibody- producing B cells. These experiments will determine whether changes in DNA binding accompany the IgM to IgG switch among anti- DNA antibodies. Finally, these experiments will determine whether somatic mutation of immunoglobulin variable region genes accompany the isotype switch. Hopefully the results from these experiments will provide new insight into the processes that operate to generate antibodies to DNA in autoimmune mice and in humans with lupus.