Studies on chicken immunoglobulin gene moditication and attinity maturation

鸡免疫球蛋白基因修饰及亲和力成熟的研究

• 批准号: 09680674
• 负责人: YAMAGISHI Hideo
• 金额: $ 2.24万
• 依托单位: Health Research Foundation (1998)Kyoto University (1997)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09680674/
• 关键词: Bursa Fabricius; Germinal center; Immunoglobulin; PCR method; Affinity maturation; Gene conversion; Point mutation; Class switch recombination; 抗体遺伝子; NPハプテン; 抗原親和性; クラススイツチ組換え; FITCハプテン; 高親和性; 体細胞突然変異; クラススイッチ領域

Chicken bursal follicles and germinal centers enabled us to analyze the bursal and postbursal diversification of B-cells due to its easy isolation and the PCR amplification of immunoglobulin genes.Antigen-independent bursal B-cell diversification by gene conversions and point mutations generated crippling mutations at the high yield of 50% before hatching but the crippling mutation ratio was dramatically decreased by antigen-dependent positive selection after hatching.Postbursal B-cells migrating into single germinal centers are further diversified by gene conversion in the early phase of germinal center reaction and are subsequently subjected to point mutations and selection for oligoclonality which may represent an intermediate step of affinity maturation.We characterized two switch regions, Smu region of 5 kb long composed of TATGG and ACCAQ pentameric repeats and S gamma region of TATGG and GGCAG repeats and showed deletional switch recombinations between these two regions.

鸡法氏囊卵泡和生发中心由于其易于分离和免疫球蛋白基因的PCR扩增，使我们能够分析b细胞的法氏囊和法氏囊后分化。不依赖抗原的法氏囊b细胞通过基因转换和点突变多样化，在孵化前产生致残突变，产量高达50%，但在孵化后通过抗原依赖的正选择，致残突变率显著降低。在生发中心反应的早期阶段，迁移到单个生发中心的囊后b细胞通过基因转换进一步多样化，随后遭受点突变和寡克隆选择，这可能是亲和成熟的中间步骤。我们发现了两个开关区，即由TATGG和ACCAQ五聚体重复序列组成的长5kb的Smu区和TATGG和GGCAG重复序列组成的S γ区，并在这两个区域之间显示了缺失的开关重组。

项目成果

山岸秀夫: "脾胚中心での免疫グロブリン多様性の増幅とB細胞レパトワ形成-自己免疫とアレルギーの誘発" Immunology Frontier. 7. 277-282 (1997)

Hideo Yamagishi：“脾生发中心免疫球蛋白多样性的扩增和 B 细胞库的形成 - 自身免疫和过敏的诱导”《免疫学前沿》7. 277-282 (1997)。

Kanari Yasuyoshi: "Uaiable gene sogment-specitic N-insentims at the signal joint of T cell receptor Vβ-Dβ recombinations" Immunology Letters. (印刷中). (1998)

Kanari Yasuyoshi：“T 细胞受体 Vβ-Dβ 重组信号接头上可用的基因片段特异性 N-insentims”（免疫学快报）（1998 年）。

山岸秀夫: "リンパ濾胎におけるB細胞レパトワ形成機構" 臨床免疫. 31・5 印刷中. (1999)

Hideo Yamagishi：“淋巴过滤中 B 细胞库形成的机制”临床免疫学 31・5 出版中（1999 年）。

Arakawa Hiroshi: "Oligoclonal development of B-cells bearing discrete Ig chains in chicken single gorminal centers" Journal of Immunology. 160. 4232-4241 (1998)

荒川浩 (Arakawa Hiroshi)：“鸡单一生殖中心中携带离散 Ig 链的 B 细胞的寡克隆发育”《免疫学杂志》。

Arakawa, H., Kuma, K., Yasuda, M., Furusawa, S., Ekino, S.and Yamagishi, H.: "Oligoclonal development of B cells bearing discrete Ig chains in chicken germinal centers." J.Immunol.160. 4232-4241 (1998)

Arakawa, H.、Kuma, K.、Yasuda, M.、Furusawa, S.、Ekino, S. 和 Yamagishi, H.：“鸡生发中心中带有离散 Ig 链的 B 细胞的寡克隆发育。”