Teleost IgD+IgM− B Cells Mount Clonally Expanded and Mildly Mutated Intestinal IgD Responses in the Absence of Lymphoid Follicles

Abstract

Summary: Immunoglobulin D (IgD) is an ancient antibody with dual membrane-bound and fluid-phase antigen receptor functions. The biology of secreted IgD remains elusive. Here, we demonstrate that teleost IgD+IgM− plasmablasts constitute a major lymphocyte population in some mucosal surfaces, including the gut mucosa. Remarkably, secreted IgD binds to gut commensal bacteria, which in turn stimulate IgD gene transcription in gut B cells. Accordingly, secreted IgD from gut as well as gill mucosae, but not the spleen, show a V(D)J gene configuration consistent with microbiota-driven clonal expansion and diversification, including mild somatic hypermutation. By showing that secreted IgD establishes a mutualistic relationship with commensals, our findings suggest that secreted IgD may play an evolutionary conserved role in mucosal homeostasis. : Perdiguero et al. show that IgD+IgM− plasmablasts constitute a major lymphocyte population in the teleost intestine, as in gills. In these two tissues, IgD molecular signatures reflect a clonal expansion not detected in the spleen. Finally, secreted IgD in the intestine establishes a two-way interaction with the local microbiota. Keywords: IgD, teleost fish, intestine, gills, microbiota, B cells, clonal expansion, somatic hypermutation, SHM