Clonal persistence dominates homeostatic intestinal IgA responses

Abstract

Immunoglobulin A (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. However, we lack a detailed understanding of how IgA responses are temporally integrated across inductive and effector sites. Here, we dissect homeostatic IgA responses from the perspective of clonal repertoires in inductive compartments and the gut lamina propria as the main effector compartment. We show that unique clonal patterns dominate across gut inductive sites and that plasma cell (PC) clones in gut lamina propria entail progressive stages of differentiation. We demonstrate that ongoing diversification of recurrent clones continuously seeds the gut PC 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.

Keywords: BCR repertoire; IgA; Peyer’s patches; germinal center; gut; mucosal immunology; plasma cells.