B cell function in mice transgenic for mCTLA4-H gamma 1: lack of germinal centers correlated with poor affinity maturation and class switching despite normal priming of CD4+ T cells.
B cell function in mice transgenic for mCTLA4-H gamma 1: lack of germinal centers correlated with poor affinity maturation and class switching despite normal priming of CD4+ T cells.
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DOI：
10.1084/jem.179.3.819
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发表时间：
1994-03-01
期刊：
影响因子：
--
通讯作者：
Kosco-Vilbois M
中科院分区：
文献类型：
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作者：
Lane P;Burdet C;Hubele S;Scheidegger D;Müller U;McConnell F;Kosco-Vilbois M
本报告概述了过表达小鼠ctla -4-人γ 1 （mCTLA4-H γ 1）蛋白的转基因小鼠的B细胞表型。尽管事实上这些小鼠启动CD4+ T细胞（Ronchese， F.， B. Housemann， S. Hubele和P. Lane. 1994）。J. Exp. Med. 179:809)，抗体对t依赖性抗原的反应严重受损。相反，T独立反应是正常的，这表明mCTLA4-H γ 1不直接作用于B细胞，而是通过损害T细胞的帮助间接起作用。受损的抗体缺陷与受损的类转换、低总免疫球蛋白（Ig）G和抗原特异性IgG反应以及脾脏和淋巴结中没有生发中心形成有关，但在肠道相关组织中没有。与正常小鼠相比，由转基因小鼠制成的杂交瘤的生发中心形成缺陷与体细胞突变程度的降低有关。mCTLA4-H γ 1似乎可能通过阻断T细胞和B细胞之间的相互作用来发挥其作用，从而诱导T细胞帮助B细胞。
This report outlines the B cell phenotype of transgenic mice that overexpresses the mouse CTLA-4-human gamma 1 (mCTLA4-H gamma 1) protein. Despite the fact that these mice prime CD4+ T cells (Ronchese, F., B. Housemann, S. Hubele, and P. Lane. 1994. J. Exp. Med. 179:809), antibody responses to T-dependent antigens are severely impaired. In contrast, T-independent responses are normal which suggests mCTLA4-H gamma 1 does not act directly on B cells, but acts indirectly by impairing T cell help. The impaired antibody defect is associated with impaired class switching, with low total immunoglobulin (Ig)G and antigen-specific IgG responses, and an absence of germinal center formation in spleen and lymph nodes but not gut-associated tissues. The defective germinal center formation is associated with a reduction in the degree of somatic mutation in hybridomas made from transgenic mice in comparison with those made from normal mice. It seems likely that mCTLA4-H gamma 1 exerts its effect by blocking an interaction between T and B cells that induce T cell help for B cells.