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B cell maintenance of subcapsular sinus macrophages protects against a fatal viral infection independent of adaptive immunity.

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) ?1?2, 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 LT?1?2 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.

SUBMITTER: Moseman EA

PROVIDER: S-EPMC3359130 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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B cell maintenance of subcapsular sinus macrophages protects against a fatal viral infection independent of adaptive immunity.

Moseman E Ashley EA Iannacone Matteo M Bosurgi Lidia L Tonti Elena E Chevrier Nicolas N Tumanov Alexei A Fu Yang-Xin YX Hacohen Nir N von Andrian Ulrich H UH

Immunity 20120301 3

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 ...[more]

PMID: 22386268

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B cell maintenance of subcapsular sinus macrophages protects against a fatal viral infection independent of adaptive immunity.

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B cell maintenance of subcapsular sinus macrophages protects against a fatal viral infection independent of adaptive immunity.

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