TRAF6 Is Required for Generation of the B-1a B Cell Compartment as well as T Cell-Dependent and -Independent Humoral Immune Responses
TRAF6 Is Required for Generation of the B-1a B Cell Compartment as well as T Cell-Dependent and -Independent Humoral Immune Responses
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DOI：
10.1371/journal.pone.0004736
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发表时间：
2009-03-09
期刊：
影响因子：
3.7
通讯作者：
Choi, Yongwon
中科院分区：
文献类型：
--
作者：
Kobayashi, Takashi;Kim, Tae Soo;Choi, Yongwon
TNF受体超家族成员，如CD40和toll样受体（TLRs），调节B细胞分化和激活的许多方面。TRAF6是这些受体的细胞内信号接头分子，但其在B细胞中的作用尚未被先前的遗传方法阐明，因为TRAF6基因的系统性缺失会导致围产期死亡。本研究表明，B细胞特异性TRAF6缺乏导致骨髓和脾脏中成熟B细胞数量减少。以同型转换和长寿命浆细胞生成为特征的最佳T细胞依赖（TD）抗原反应在B细胞特异性traf6缺陷小鼠中也受到损害。B细胞特异性traf6缺陷小鼠也表现出较低的血清IgM和IgG2b水平，以及对T细胞非依赖性（TI）抗原反应的抗原特异性IgM产生缺陷。出乎意料的是，traf6缺陷的B细胞祖细胞不能产生CD5(+) B-1细胞。这些结果揭示了TRAF6在TD和TI体液免疫应答和诱导命运决定中所起的关键作用，这些决定是产生B-1 B细胞室所必需的。
TNF receptor superfamily members, such as CD40 and the Toll-like receptors (TLRs), regulate many aspects of B cell differentiation and activation. TRAF6 is an intracellular signaling adaptor molecule for these receptors, but its role in B cells has not been clarified by previous genetic approaches, as the systemic deletion of the TRAF6 gene results in perinatal lethality. Here we show that B cell-specific TRAF6 deficiency results in a reduced number of mature B cells in the bone marrow and spleen. Optimal T cell-dependent (TD) antigen responses, as characterized by isotype switching and long-lived plasma cell generation, are also impaired in B cell-specific TRAF6-deficient mice. B cell-specific TRAF6-deficient mice also exhibit lower levels of serum IgM and IgG2b and defective antigen-specific IgM production in response to T cell-independent (TI) antigens. Unexpectedly, TRAF6-deficient B cell progenitors are unable to generate CD5(+) B-1 cells. These results reveal critical roles for TRAF6 in TD and TI humoral immune responses and in inductive fate decisions necessary to generate the B-1 B cell compartment.