Role of commensal bacteria in development of gut-associated lymphoid tissues and preimmune antibody repertoire
Role of commensal bacteria in development of gut-associated lymphoid tissues and preimmune antibody repertoire
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DOI：
10.4049/jimmunol.172.2.1118
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发表时间：
2004-01-15
影响因子：
4.4
通讯作者：
Knight, KL
中科院分区：
文献类型：
--
作者：
Rhee, KJ;Sethupathi, P;Knight, KL
肠道细菌是肠道相关淋巴组织（GALT）发育所必需的，它介导多种宿主免疫功能，例如粘膜免疫和口服耐受。在兔子中，肠道微生物群也是通过促进已迁移至 GALT 的 B 细胞中 Ig 基因的体细胞多样化来形成免疫前抗体库所必需的。我们研究了细菌诱导 GALT 发育的机制。将细菌引入通过显微手术使阑尾无菌的兔子体内（我们将这些兔子称为无菌阑尾兔）。然后我们确定了促进 GALT 发育的肠道菌群的特定成员。脆弱拟杆菌和枯草芽孢杆菌的组合持续促进 GALT 发育，并导致免疫前抗体库的发育，如阑尾 B 细胞中 VDJ-Cmu 基因体细胞多样性的增加所示。无论是单独的物种，还是亚末端梭状芽胞杆菌、大肠杆菌或表皮葡萄球菌，都不能持续诱导 GALT 发育。脆弱拟杆菌本身具有免疫原性，不会促进 GALT 发育；因此，兔子的 GALT 发育似乎不是 Ag 特异性免疫反应的结果。为了确定 GALT 发育所需的细菌途径，我们将脆弱芽孢杆菌以及枯草芽孢杆菌的应激反应突变体引入无菌阑尾兔中。我们确定了两种 Spo0A 控制的应激反应，即孢子形成和蛋白质 YqxM 的分泌，这是 GALT 发育所需的。我们得出的结论是，共生肠道菌群的特定成员通过应激反应的特定子集驱动 GALT 发育。
Intestinal bacteria are required for development of gut-associated lymphoid tissues (GALT), which mediate a variety of host immune functions, such as mucosal immunity and oral tolerance. In rabbits, the intestinal microflora are also required for developing the preimmune Ab repertoire by promoting somatic diversification of Ig genes in B cells that have migrated to GALT. We studied the mechanism of bacteria-induced GALT development. Bacteria were introduced into rabbits in which the appendix had been rendered germfree by microsurgery (we refer to these rabbits as germfree-appendix rabbits). We then identified specific members of the intestinal flora that promote GALT development. The combination of Bacteroides fragilis and Bacillus subtilis consistently promoted GALT development and led to development of the preimmune Ab repertoire, as shown by an increase in somatic diversification of VDJ-Cmu genes in appendix B cells. Neither species alone consistently induced GALT development, nor did Clostridium subterminale, Escherichia coli, or Staphylococcus epidermidis. B. fragilis, which by itself is immunogenic, did not promote GALT development; hence, GALT development in rabbits does not appear to be the result of an Ag-specific immune response. To identify bacterial pathways required for GALT development, we introduced B. fragilis along with stress-response mutants of B. subtilis into germfree-appendix rabbits. We identified two Spo0A-controlled stress responses, sporulation and secretion of the protein YqxM, which are required for GALT development. We conclude that specific members of the commensal, intestinal flora drive GALT development through a specific subset of stress responses.