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) 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.

• Authors: E Ashley Moseman, Matteo Iannacone, Lidia Bosurgi, Elena Tonti, Nicolas Chevrier, Alexei Tumanov, Yang-Xin Fu, Nir Hacohen, Ulrich H von Andrian
• Journal: Immunity (Immunity) Vol. 36 Issue 3 Pg. 415-26 (Mar 23 2012) ISSN: 1097-4180 [Electronic] United States
• PMID: 22386268 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

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

Topics

• 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, pathogenicity)