Tunable dynamics of B cell selection in gut germinal centers.

Abstract B lymphocytes are central to maintaining balanced enteric responses through production of immunoglobulins (Igs). A large fraction of Igs are produced in germinal center (GC) responses, which form upon immunization or infection in the majority of secondary lymphoid organs, but are constitutively present in gut-associated lymphoid tissue. However, the ontogeny and antigenic drivers of constitutive gut-associated GCs were poorly understood. Using a multicolor fate-mapping approach with the Confetti fluorescent allele to visualize GC clonal expansions, we observed single-color GCs in the steady state intestine, suggestive of strong selection events. By coupling fate-mapping, gnotobiotics and Ig sequencing, we showed affinity-driven selection occurring in gut-associated GCs in response to members of the microbiome. We observed that these GCs persist even in the absence of microbiota, although their isotype distribution and clonal composition are altered. Furthermore, we identified several prominent public Ig clonotypes in intestinal GCs, whose presence were tuned by microbial diversity.