Infection-induced type I interferons activate CD11b on B-1 cells for subsequent lymph node accumulation

Abstract

Innate-like B-1a lymphocytes rapidly redistribute to regional mediastinal lymph nodes (MedLNs) during influenza infection to generate protective IgM. Here we demonstrate that influenza infection-induced type I interferons directly stimulate body cavity B-1 cells and are a necessary signal required for B-1 cell accumulation in MedLNs. Vascular mimetic flow chamber studies show that type I interferons increase ligand-mediated B-1 cell adhesion under shear stress by inducing high-affinity conformation shifts of surface-expressed integrins. In vivo trafficking experiments identify CD11b as the non-redundant, interferon-activated integrin required for B-1 cell accumulation in MedLNs. Thus, CD11b on B-1 cells senses infection-induced innate signals and facilitates their rapid sequester into secondary lymphoid tissues, thereby regulating the accumulation of polyreactive IgM producers at sites of infection. Tissue-resident B-1 cells express CD11b, unlike their lymphoid organ-residing counterparts. Here the authors show that influenza-induced type I interferons activate CD11b on B-1 cells, facilitating entry to mediastinal lymph nodes, where they provide the first line of antibody-mediated host defense.