Wei Bo, Su Thomas T, Dalwadi Harnisha, Stephan Robert P, Fujiwara Daisuke, Huang Tiffany T, Brewer Sarah, Chen Lindy, Arditi Moshe, Borneman James, Rawlings David J, Braun Jonathan
Department of Pathology and Laboratory Medicine, UCLA David Geffen School of Medicine, Los Angeles, CA 90095-1732, USA.
Eur J Immunol. 2008 Dec;38(12):3411-25. doi: 10.1002/eji.200838432.
Since enteric microbial composition is a distinctive and stable individual trait, microbial heterogeneity may confer lifelong, non-genetic differences between individuals. Here we report that C57BL/6 mice bearing restricted flora microbiota, a distinct but diverse resident enteric microbial community, are numerically and functionally deficient in marginal zone (MZ) B cells. Surprisingly, MZ B-cell levels are minimally affected by germ-free conditions or null mutations of various TLR signaling molecules. In contrast, MZ B-cell depletion is exquisitely dependent on cytolytic CD8(+) T cells, and includes targeting of a cross-reactive microbial/endogenous MHC class 1B antigen. Thus, members of certain enteric microbial communities link with CD8(+) T cells as a previously unappreciated mechanism that shapes innate immunity dependent on innate-like B cells.
由于肠道微生物组成是一种独特且稳定的个体特征,微生物异质性可能导致个体之间存在终身的、非遗传的差异。在此,我们报告称,携带受限菌群微生物群(一种独特但多样的常驻肠道微生物群落)的C57BL/6小鼠在边缘区(MZ)B细胞的数量和功能上存在缺陷。令人惊讶的是,MZ B细胞水平受无菌条件或各种Toll样受体(TLR)信号分子的无效突变影响极小。相反,MZ B细胞的耗竭完全依赖于细胞毒性CD8(+) T细胞,并且包括对一种交叉反应性微生物/内源性MHC 1B类抗原的靶向作用。因此,某些肠道微生物群落的成员与CD8(+) T细胞相联系,这是一种以前未被认识到的塑造依赖于固有样B细胞的先天免疫的机制。