Induction of commensal-specific immunity contributes to tissue homeostasis, yet the mechanisms underlying induction of commensal-specific B cells remain poorly understood in part due to a lack of tools to identify these cells. Using phage display, we identified segmented filamentous bacteria (SFB) antigens targeted by serum and intestinal antibodies and generated B cell tetramers to track SFB-specific B cells in gut-associated lymphoid tissues. We revealed a compartmentalized response in SFB-specific B cell activation, with a gradient of immunoglobulin A (IgA), IgG1, and IgG2b isotype production along Peyer’s patches contrasted by selective production of IgG2b within mesenteric lymph nodes. V(D)J sequencing and monoclonal antibody generation identified somatic hypermutation driven affinity maturation to SFB antigens under homeostatic conditions. Combining phage display and B cell tetramers will enable investigation of the ontogeny and function of commensal-specific B cell responses in tissue immunity, inflammation, and repair.

共生特异性免疫的诱导有助于组织稳态，但由于缺乏识别这些细胞的工具，诱导共生特异性 B 细胞的机制仍知之甚少。利用噬菌体展示，我们鉴定了血清和肠道抗体靶向的分段丝状细菌 (SFB) 抗原，并生成了 B 细胞四聚体来追踪肠道相关淋巴组织中的 SFB 特异性 B 细胞。我们揭示了 SFB 特异性 B 细胞激活中的区室化反应，沿派尔集结产生免疫球蛋白 A (IgA)、IgG1 和 IgG2b 同种型的梯度，与肠系膜淋巴结内选择性产生 IgG2b 形成对比。 V(D)J 测序和单克隆抗体生成鉴定了体内平衡条件下体细胞超突变驱动的 SFB 抗原亲和力成熟。将噬菌体展示和 B 细胞四聚体相结合将能够研究共生特异性 B 细胞反应在组织免疫、炎症和修复中的个体发育和功能。