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.
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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)
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Copyright | Copyright © 2012 Elsevier Inc. All rights reserved. |
Chemical References |
- Antibodies, Neutralizing
- Antibodies, Viral
- Interferon Type I
- Lymphotoxin alpha1, beta2 Heterotrimer
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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)
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