Conjoined ontogeny of the B cell receptor repertoire and microbiome in mice

The immune system matures throughout childhood to achieve full functionality in protecting our bodies against threats. The immune system has a strong reciprocal symbiosis with the host bacterial population and the two systems co-develop, shaping each other. Despite their fundamental role in health physiology, the conjoined ontogeny of these systems is poorly characterized. Here, we study the development of B cell repertoire by analysing high throughput sequencing of their receptors in several time points of young mice. In parallel, we explored the development of the gut microbiome. We discovered that gut IgA repertoires change throughout childhood, including an increase in complementary determining region 3 (CDR3) lengths and somatic hypermutation (SHM) levels. This is in contrast to the spleen IgM repertoires that remain stable and distinct from the IgA repertoires in the gut. We also quantified the associations between diversity indices of the B cell repertoires and the microbiome, as well as correlations between bacterial and B cell receptor clusters. Our results shed light on the conjoined ontogeny of the adaptive immune system and the microbiome, providing a baseline for future research.

免疫系统在整个儿童期持续成熟，最终获得保护机体抵御各类威胁的完整功能。免疫系统与宿主细菌种群存在紧密的互惠共生关系，二者协同发育、相互塑造。尽管二者在健康生理中发挥着基础性作用，但这两个系统的联合发育进程仍未得到充分表征。本研究通过对幼年小鼠多个时间点的B细胞受体（B cell receptor, BCR）进行高通量测序，分析B细胞库（B cell repertoire）的发育过程；与此同时，我们还探究了肠道微生物组（gut microbiome）的发育情况。研究发现，肠道免疫球蛋白A（immunoglobulin A, IgA）库在整个儿童期发生动态变化，具体表现为互补决定区3（complementary determining region 3, CDR3）长度与体细胞超突变（somatic hypermutation, SHM）水平的升高。这与脾脏免疫球蛋白M（immunoglobulin M, IgM）库的稳定状态形成鲜明对比，且脾脏IgM库与肠道IgA库存在显著差异。我们还定量分析了B细胞库多样性指数与微生物组之间的关联，以及细菌簇与B细胞受体簇之间的相关性。本研究结果阐明了适应性免疫系统（adaptive immune system）与微生物组的联合发育进程，为后续相关研究提供了基准参照。