B-1 B cells derive from a developmental program distinct from that of conventional B cells, through B cell receptor (BCR)-dependent positive selection of fetally derived precursors. Here, we used direct labeling of B cells reactive with the N-acetyl-D-glucosamine (GlcNAc)-containing Lancefield group A carbohydrate of Streptococcus pyogenes to study the effects of bacterial antigens on the emergent B-1 B cell clonal repertoire. The number, phenotype, and BCR clonotypes of GlcNAc-reactive B-1 B cells were modulated by neonatal exposure to heat-killed S. pyogenes bacteria. GlcNAc-reactive B-1 clonotypes and serum antibodies were reduced in germ-free mice compared with conventionally raised mice. Colonization of germ-free mice with a conventional microbiota promoted GlcNAc-reactive B-1 B cell development and concomitantly elicited clonally related IgA⁺ plasma cells in the small intestine. Thus, exposure to microbial antigens in early life determines the clonality of the mature B-1 B cell repertoire and ensuing antibody responses, with implications for vaccination approaches and schedules.

B-1 B细胞是通过发育依赖于B细胞受体（BCR）的胎儿衍生前体的阳性选择而得自不同于常规B细胞的发育程序。在这里，我们使用与含有N-乙酰基-D-葡萄糖胺（GlcNAc）的兰斯菲尔德A组化脓性链球菌碳水化合物反应的B细胞的直接标记，以研究细菌抗原对新兴B-1 B细胞克隆成分的影响。GlcNAc反应性B-1 B细胞的数量，表型和BCR克隆型是通过新生儿暴露于热灭活的化脓性链球菌来调节的。菌。与传统饲养的小鼠相比，无菌小鼠的GlcNAc反应性B-1克隆型和血清抗体降低。用常规微生物菌群对无菌小鼠的定殖促进了GlcNAc反应性B-1 B细胞的发育，并在小肠中引起了克隆相关的IgA ⁺浆细胞。因此，在生命的早期暴露于微生物抗原决定了成熟的B-1 B细胞库的克隆性并随之产生抗体反应，这对疫苗接种方法和时间表产生了影响。