TRAF2 and TRAF3 independently mediate Ig class switching driven by CD40
TRAF2 and TRAF3 independently mediate Ig class switching driven by CD40
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DOI：
10.1093/intimm/dxp013
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发表时间：
2009-04-01
影响因子：
4.4
通讯作者：
Geha, Raif S.
中科院分区：
文献类型：
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作者：
Jabara, Haifa H.;Weng, Yu;Geha, Raif S.
野生型(WT)CD40转基因可以纠正CD40(-/-)小鼠的同型开关缺陷，但不结合肿瘤坏死因子受体相关因子(TRAF)2和3的突变CD40转基因不能纠正这种缺陷。为了确定TRAF2和TRAF3在CD40激活B细胞中的单独作用，我们引入了选择性缺乏结合TRAF2(Delta TR2)、TRAF3(Delta TR3)或两者(Delta TR2，3)到CD40(-/-)小鼠B细胞的突变CD40转基因。在Delta TR2和Delta TR3小鼠中，血清IgG1和IgE水平、对亚最佳剂量T细胞依赖抗原锁孔帽状血蓝蛋白的IgG1抗体反应、生发中心形成、CD40介导的增殖、同型转换和非规范的核因子-kappaB途径的激活在Delta TR2和Delta TR3小鼠中部分降低，而在Delta TR2，3小鼠中几乎不存在。这些结果表明，TRAF2和TRAF3各自可以独立地介导CD40驱动的类开关重组(CSR)，但两者都是CD40驱动的最佳同型开关所必需的。
The isotype switch defect in CD40(-/-) mice is corrected by wild-type (WT) CD40 transgene, but not by a mutant CD40 transgene that does not bind tumor necrosis factor receptor-associated factors (TRAF) 2 and 3. To define the individual roles of TRAF2 and TRAF3 in CD40 activation of B cells, we introduced mutant CD40 transgenes that selectively lack the ability to bind TRAF2 (Delta TR2), TRAF3 (Delta TR3) or both (Delta TR2,3) into B cells of CD40(-/-) mice. Serum IgG1 and IgE levels, IgG1 antibody response to sub-optimal doses of the T cell-dependent antigen keyhole limpet hemocyanin, germinal center formation, CD40-mediated proliferation, isotype switching and activation of the non-canonical NF-kappa B pathway were partially diminished in Delta TR2 and Delta TR3 mice and virtually absent in Delta TR2,3 mice. These results suggest that TRAF2 and TRAF3 can each independently mediate class switch recombination (CSR) driven by CD40, but both are required for optimal CD40-driven isotype switching.