Marginal zone (MZ) B cells are one of the main actors of T-independent (TI) responses in mice. To identify the B cell subset(s) involved in such responses in humans, we vaccinated healthy individuals with Pneumovax, a model TI vaccine. By high-throughput repertoire sequencing of plasma cells (PCs) isolated 7 days after vaccination and of different B cell subpopulations before and after vaccination, we show that the PC response mobilizes large clones systematically, including an immunoglobulin M component, whose diversification and amplification predated the pneumococcal vaccination. These clones could be mainly traced back to MZ B cells, together with clonally related IgA + and, to a lesser extent, IgG + CD27 + B cells. Recombinant monoclonal antibodies isolated from large PC clones recognized a wide array of bacterial species from the gut flora, indicating that TI responses in humans largely mobilize MZ and switched B cells that most likely prediversified during mucosal immune responses against bacterial antigens and acquired pneumococcal cross-reactivity through somatic hypermutation.

中文翻译：

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人体对多糖的非 T 依赖性反应动员边缘区 B 细胞针对肠道细菌抗原进行预多样化

边缘区 (MZ) B 细胞是小鼠 T 独立 (TI) 反应的主要参与者之一。为了确定参与人类此类反应的 B 细胞亚群，我们给健康个体接种了 Pneumovax（一种 TI 疫苗模型）。通过对疫苗接种后 7 天分离的浆细胞 (PC) 以及疫苗接种前后不同 B 细胞亚群进行高通量谱测序，我们发现 PC 反应系统地动员了大克隆，包括免疫球蛋白 M 成分，其多样化和扩增早于肺炎球菌疫苗接种。这些克隆主要可追溯到 MZ B 细胞，以及克隆相关的 IgA+以及，在较小程度上，IgG+CD27+B细胞。从大型 PC 克隆中分离出的重组单克隆抗体可识别肠道菌群中的多种细菌种类，表明人类的 TI 反应主要动员 MZ 和转换 B 细胞，这些细胞很可能在针对细菌抗原的粘膜免疫反应期间发生预多样化，并获得了肺炎球菌交叉反应性通过体细胞超突变。