Analysis of V(D)J recombination by RAGs expressed in mature B cells.

成熟 B 细胞中表达的 RAG 进行的 V(D)J 重组分析。

• 批准号: 10833003
• 负责人: OHMORI Hitoshi
• 金额: $ 2.11万
• 依托单位: OKAYAMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10833003/
• 关键词: germinal center; mature B cells; RAG genes; IL-7 receptor; transgenic mice; V(D)J recombination

V(D)J combination of Ig genes established in premature B cells has been thought to be conserved throughout differentiation at mature stages. However, germinal center (GC) B cells have been shown to reexpress RAG-1 and RAG-2 proteins in immunized mice. Here, we present several lines of evidence indicating that RAG proteins thus induced are functional as the V(D)J recombinase. DNA excision product reflecting Vλ1-to -Jλ1 rearrangement was generated in parallel with the expression of RAG genes in mature mouse B cells that were activated in vitro with LPS and IL-4. Similar λ chain gene rearrangement was observed in the draining lymph node of immunized mice. Further, B cells that underwent λ gene rearrangement were shown by in situ PCR to be localized within GCs. Thus, secondary rearrangement of Ig genes (receptor editing) can occur in mature B cells.

在未成熟B细胞中建立的IG基因的V（D）J组合被认为在成熟阶段的整个分化过程中是保守的。然而，已显示生殖中心（GC）B细胞在免疫小鼠中重新表达RAG-1和RAG-2蛋白。在这里，我们提出了几条证据，表明由此诱导的RAG蛋白具有V（D）J重组酶的功能。在用LPS和IL-4体外活化的成熟小鼠B细胞中，产生反映Vλ1-至-Jλ1重排的DNA切除产物，同时产生RAG基因的表达。在免疫小鼠的引流淋巴结中观察到类似的λ链基因重排。此外，原位PCR显示经历λ基因重排的B细胞定位于GC内。因此，IG基因的二级重排（受体编辑）可在成熟B细胞中发生。

项目成果

Masaki Hikida: "Rerrangement of λ light chain genes in mature B cells in vitro and in vivo. Function of reexpressed recombination-activating gene (RAG) products."Journal of Experimental Medicine. Vol.187. 795-799 (1998)

Masaki Hikida：“成熟 B 细胞中 λ 轻链基因的体外和体内重排。重新表达的重组激活基因 (RAG) 产物的功能。”实验医学杂志第 795-799 卷（1998 年）。

Hitoshi Ohmori: "Expression and function of recombination activating genes in mature B cells."Critical Reviews in Immunology. 18. 221-235 (1998)

Hitoshi Ohmori：“成熟 B 细胞中重组激活基因的表达和功能。”免疫学批判评论。

Masaki Hikida: "Expression of recombination activating genes in germinal center B cells : involvement of interleukin 7 (IL-7) and the IL-7 receptor."Journal of Experimental Medicine. Vol.188. 365-372 (1998)

Masaki Hikida：“重组激活基因在生发中心 B 细胞中的表达：白细胞介素 7 (IL-7) 和 IL-7 受体的参与。”实验医学杂志。

Masaki Hikida: "Expression of recombination activating genes in germinal center B cells : involvement of interleukin 7 (IL-7) and the IL-7 receptor."Journal of Experimental Medicine. 188. 365-372 (1998)

Masaki Hikida：“重组激活基因在生发中心 B 细胞中的表达：白细胞介素 7 (IL-7) 和 IL-7 受体的参与。”实验医学杂志。

大森 斉: "肺中心におけるRAG遺伝子発現とその生理的意義"Immunology Frontier. 9巻2号. 15-21 (1999)

Hitoshi Omori：“肺中枢的 RAG 基因表达及其生理意义”《免疫学前沿》，第 9 卷，第 2. 15-21 期（1999 年）。