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

Elizabeth E. Waffarn,Christine J. Hastey,Scott I. Simon,Youn Soo Choi,Ulrich Kalinke,Simon Cherry,Neha Dixit,Nicole Baumgarth

doi:10.1038/ncomms9991

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.

Highlights

Innate-like B-1a lymphocytes rapidly redistribute to regional mediastinal lymph nodes (MedLNs) during influenza infection to generate protective IgM
To understand the mechanisms by which B-1a cells are drawn to the site of infection, we determined the kinetics with which infection-induced antigenindependent signals activate B-1 cells to accumulate within MedLN
Together with the nearly 10-fold increases in MedLN cellularity compared with pre-infection levels, this demonstrated an early and selective accumulation of B-1a cells in the MedLN after influenza virus infection as shown previously[20]

Summary

Introduction

Innate-like B-1a lymphocytes rapidly redistribute to regional mediastinal lymph nodes (MedLNs) during influenza infection to generate protective IgM. In vivo trafficking experiments identify CD11b as the non-redundant, interferon-activated integrin required for B-1 cell accumulation in MedLNs. 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. B-1 cells are innate-like participants in immune responses within secondary lymphoid tissues. In response to pathogenic insult, B-1 cells move from their primary location within the peritoneal and pleural cavities to secondary lymphoid tissues such as the spleen and lymph nodes and begin to secrete IgM. B-1 cells redistribute to regional mediastinal lymph nodes (MedLN) to become a primary source of locally secreted IgM20. While the selective expression of CD11b suggests its role in regulating B-1 cell migration, CD11b gene-targeted mice have normal numbers of peritoneal cavity B-1 cells

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