Immunity
Volume 36, Issue 3, 23 March 2012, Pages 415-426
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Article
B Cell Maintenance of Subcapsular Sinus Macrophages Protects against a Fatal Viral Infection Independent of Adaptive Immunity

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Summary

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.

Highlights

► B cell-derived lymphotoxin α1β2 induces and maintains SCS macrophages ► Lymphotoxin α1β2 renders SCS macrophages permissive to productive VSV infection ► SCS macrophage infection by VSV is essential for neuroprotective IFN-I production ► Antibodies and cell-mediated immunity are dispensable for protection against VSV

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These authors contributed equally to this work