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

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.

Graphical Abstract

Highlights

• •

  IgD ⁺IgM ⁻ B cells constitute the main non-IgT B cell subset in rainbow trout guts

• •

  Gut IgD responses establish a two-way interaction with the local microbiota

• •

  Mucosal but not splenic IgD undergoes clonal expansion and diversification

• •

  Despite the lack of germinal centers, mucosal IgD is mildly mutated in rainbow trout

Abstract

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.