Origin of class-specific anti-DNA antibodies

类别特异性抗 DNA 抗体的起源

• 批准号: 03670183
• 负责人: HIROSE Sachiko
• 金额: $ 1.28万
• 依托单位: Juntendo University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03670183/
• 关键词: anti-DNA antibodies; systemic lupus erythematosus; somatic mutation; immunoglobulin variable region; class-switch; clonal proliferation; New Zealand mice; CD5B細胞; New Zealand マウス; 全身性エリテマト-デス; 免疫グロブリン遺伝子; ハイブリド-マ

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.

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。

项目成果

広瀬幸子: "自己免疫とトレランス" 中外医学社, 11 (1993)

广濑幸子：“自身免疫和耐受性”中外医学社，11（1993）

Katsutoshi Tokushige: "Genetic association between natural autoantibody responses to histones and DNA in murine lupus." Autoimmunity.

Katsutoshi Tokushige：“小鼠狼疮中组蛋白和 DNA 的天然自身抗体反应之间的遗传关联。”

Toshikazu Shirai: "CD5^+ B cells in autoimmune disease and lymphoid malignancy." Clin.Immunol.Immunopathol.59. 173-186 (1991)

Toshikazu Shirai：“自身免疫性疾病和淋巴恶性肿瘤中的 CD5^ B 细胞。”

Hiroyuki Nishimura: "E_β^z of NZW mice is identical to E_β^u of B10.PL mice." Immunogenetics. 33. 413-414 (1991)

Hiroyuki Nishimura：“NZW 小鼠的 E_β^z 与 B10.PL 小鼠的 E_β^u 相同。” 33. 413-414 (1991)

Nishimura,H. et al.: "Differential expression of three CD45 alternative structures on murine T cells : exon 6-dependent epitope as a marker for functional heterogeneity of CD4^+ T cells" Int. Immunol.4. 923-930 (1992)

西村，H.