Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA; National Institutes of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Immunity. 2020 Jul 14;53(1):172-186.e6. doi: 10.1016/j.immuni.2020.06.006. Epub 2020 Jun 30.
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 细胞来源于与传统 B 细胞不同的发育程序，通过 B 细胞受体（BCR）依赖性的胎儿来源前体的阳性选择。在这里，我们使用对反应 N-乙酰-D-氨基葡萄糖（GlcNAc）的 B 细胞进行直接标记，该物质含有化脓性链球菌的 Lancefield 组 A 碳水化合物，以研究细菌抗原对新兴的 B-1 B 细胞克隆库的影响。新生儿接触热灭活的化脓性链球菌细菌会调节 GlcNAc 反应性 B-1 B 细胞的数量、表型和 BCR 克隆型。与常规饲养的小鼠相比，无菌小鼠中的 GlcNAc 反应性 B-1 克隆型和血清抗体减少。无菌小鼠定植常规微生物群会促进 GlcNAc 反应性 B-1 B 细胞的发育，并同时在小肠中引发克隆相关的 IgA 浆细胞。因此，生命早期接触微生物抗原决定了成熟的 B-1 B 细胞库的克隆性和随后的抗体反应，这对疫苗接种方法和方案有影响。
