Clonal persistence dominates homeostatic intestinal IgA responses

IgA is the most abundantly produced antibody isotype and mediates protection and homeostatic regulation at mucosal surfaces. Steady state IgA production is supported by multiple pathways, including chronic germinal centers in gut inductive lymphoid tissues, but we lack a detailed understanding of how IgA responses are integrated across inductive and effector sites, and in time. Here, we dissect homeostatic IgA responses from the perspective of clonal repertoires in inductive compartments and the gut lamina propria as main effector compartment. We show that unique clonal patterns dominate across gut inductive sites and that plasma cell clones in gut lamina propria entail progressive stages of differentiation. We demonstrate that ongoing diversification of recurrent clones continuously seeds the gut plasma cell population. These observations suggest that clonal rather than cellular longevity shapes IgA responses and that dynamic modulation of recurrent clones may balance stability and flexibility of the gut PC repertoire.

免疫球蛋白A（IgA）是机体产生量最为丰富的抗体亚型，可介导黏膜表面的免疫保护与稳态调控。稳态下的IgA产生依赖多条通路，包括肠道诱导性淋巴组织中的慢性生发中心，但目前我们尚不清楚IgA应答如何在诱导位点与效应位点之间，并随时间进程完成整合。本研究以诱导性区室的克隆谱（clonal repertoires），以及作为核心效应区室的肠道固有层为视角，解析稳态IgA应答。研究发现，肠道诱导位点以独特的克隆模式为主导，而肠道固有层内的浆细胞（plasma cell, PC）克隆伴随渐进式的分化阶段。本研究证实，复发性克隆的持续多样化可持续为肠道浆细胞群体注入新的克隆。上述观察结果表明，决定IgA应答特征的是克隆寿命而非细胞寿命；且对复发性克隆的动态调控，或可平衡肠道浆细胞克隆谱的稳定性与灵活性。