Differentiation of plasma cells (PCs) and the production of antibodies are the backbone of adaptive humoral immunity. The most commonly produced antibody isotype is immunoglobulin (Ig) A, with monomeric IgA predominating in the blood and polymeric IgA in mucosal secretions. Polymeric IgA binds to the polymeric Ig receptor, mediating transepithelial IgA transport and secretion into mucosal fluids such as saliva, tears, breast milk, bile and intestinal secretions. Within these mucosal secretions, secretory IgA (SIgA) functions as a barrier to pathogens and toxins and regulates the microbiota at the intestinal mucosal surface. However, we lack a detailed understanding of how IgA responses are temporally integrated across inductive and effector sites.

We characterized steady-state gut B cell responses in inductive compartments and the gut PC population at cellular resolution over time and space. We showed that unique clonal patterns in the B cell compartment dominated within gut inductive sites that differ in relative expansion and somatic mutations from the gut PC population. Gut PC clones encompassed progressive stages of differentiation, reminiscent of the situation in the bone marrow and exhibiting signatures of newly generated, short-lived, and long-lived PCs. Fate tracking of activation-induced cytidine deaminase (AID)-expressing B cells from inductive sites to the gut lamina propria showed that ongoing diversification of recurrent clones continuously seeded the gut PC population. I will discuss how these observations may integrate key findings in the field and explain how gut B cell responses generate IgA responses against gut microbiota.