美国阿拉巴马大学伯明翰分校R. Glenn King和John F. Kearney课题组合作取得一项新成果。他们发现暴露于共生菌衍生抗原的新生儿会促进多糖特异性B-1 B细胞库的形成。这一研究成果在线发表在2020年6月30日出版的《免疫学》上。

研究人员使用与含有化脓性链球兰斯菲尔德A组碳水化合物N-乙酰基-D-葡萄糖胺（GlcNAc）的直接反应标记了B细胞，以研究细菌抗原对新兴B-1 B细胞克隆群的影响。GlcNAc反应性B-1 B细胞的数量、表型和B细胞受体（BCR）克隆型受到新生儿暴露于热灭活化脓性链球菌的调控。

与传统饲养小鼠相比，无菌小鼠的GlcNAc反应性B-1克隆型和血清抗体水平降低。对无菌小鼠定殖典型微生物菌群促进了GlcNAc反应性B-1 B细胞的发育，并在小肠中诱导了克隆相关的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都有影响。

据了解，B-1 B细胞的发育不同于常规B细胞的发育，其发育依赖于BCR胎儿衍生前体的阳性选择。

附：英文原文

Title: Neonatal Exposure to Commensal-Bacteria-Derived Antigens Directs Polysaccharide-Specific B-1 B Cell Repertoire Development

Author: J. Stewart New, Brian L.P. Dizon, Christopher F. Fucile, Alexander F. Rosenberg, John F. Kearney, R. Glenn King

Issue&Volume: 2020-06-30

Abstract: B-1 B cells derive from a developmental program distinct from that of conventionalB cells, through B cell receptor (BCR)-dependent positive selection of fetally derivedprecursors. 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 modulatedby neonatal exposure to heat-killed S. pyogenes bacteria. GlcNAc-reactive B-1 clonotypes and serum antibodies were reduced in germ-freemice compared with conventionally raised mice. Colonization of germ-free mice witha conventional microbiota promoted GlcNAc-reactive B-1 B cell development and concomitantlyelicited clonally related IgA+ plasma cells in the small intestine. Thus, exposure to microbial antigens in earlylife determines the clonality of the mature B-1 B cell repertoire and ensuing antibodyresponses, with implications for vaccination approaches and schedules.

DOI: 10.1016/j.immuni.2020.06.006

Source: https://www.cell.com/immunity/fulltext/S1074-7613(20)30236-3