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

Immunity. 2012 Mar 23;36(3):415-26. doi: 10.1016/j.immuni.2012.01.013. Epub 2012 Mar 1.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • Animals
  • Antibodies, Neutralizing / metabolism
  • Antibodies, Viral / metabolism
  • B-Lymphocytes / immunology*
  • Immunity, Innate
  • Interferon Type I / biosynthesis
  • Lymph Nodes / immunology
  • Lymphotoxin alpha1, beta2 Heterotrimer / metabolism
  • Macrophages / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Signal Transduction / immunology
  • Vesicular Stomatitis / immunology*
  • Vesiculovirus / immunology
  • Vesiculovirus / pathogenicity


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Interferon Type I
  • Lymphotoxin alpha1, beta2 Heterotrimer