B Cell Maintenance of Subcapsular Sinus Macrophages Protects Against a Fatal Viral Infection Independent of Adaptive Immunity

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2012 Mar 6

PMID 22386268

Citations 98

Authors

E Ashley Moseman

Matteo Iannacone

Lidia Bosurgi

Elena Tonti

Nicolas Chevrier

Alexei Tumanov

Yang-Xin Fu

Nir Hacohen

Ulrich H von Andrian

Affiliations

Soon will be listed here.

Abstract

Neutralizing antibodies have been thought to be required for protection against acutely cytopathic viruses, such as the neurotropic vesicular stomatitis virus (VSV). Utilizing mice that possess B cells but lack antibodies, we show here that survival upon subcutaneous (s.c.) VSV challenge was independent of neutralizing antibody production or cell-mediated adaptive immunity. However, B cells were absolutely required to provide lymphotoxin (LT) α1β2, which maintained a protective subcapsular sinus (SCS) macrophage phenotype within virus draining lymph nodes (LNs). Macrophages within the SCS of B cell-deficient LNs, or of mice that lack LTα1β2 selectively in B cells, displayed an aberrant phenotype, failed to replicate VSV, and therefore did not produce type I interferons, which were required to prevent fatal VSV invasion of intranodal nerves. Thus, although B cells are essential for survival during VSV infection, their contribution involves the provision of innate differentiation and maintenance signals to macrophages, rather than adaptive immune mechanisms.

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