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

E. Ashley Moseman, Matteo Iannacone, Lidia Bosurgi, Elena Tonti, Nicolas Chevrier, Alexei Tumanov, Yang Xin Fu, Nir Hacohen, Ulrich H. von Andrian

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)415-426
Number of pages12
JournalImmunity
Volume36
Issue number3
DOIs
Publication statusPublished - Mar 23 2012

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this

Moseman, E. A., Iannacone, M., Bosurgi, L., Tonti, E., Chevrier, N., Tumanov, A., Fu, Y. X., Hacohen, N., & von Andrian, U. H. (2012). B Cell Maintenance of Subcapsular Sinus Macrophages Protects against a Fatal Viral Infection Independent of Adaptive Immunity. Immunity, 36(3), 415-426. https://doi.org/10.1016/j.immuni.2012.01.013