title: 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.affiliation: Immune Disease Institute and Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: E Ashley
authors.initials: EA
authors.lastname: Moseman
authors.forename: Matteo
authors.initials: M
authors.lastname: Iannacone
authors.forename: Lidia
authors.initials: L
authors.lastname: Bosurgi
authors.forename: Elena
authors.initials: E
authors.lastname: Tonti
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chevrier
authors.forename: Alexei
authors.initials: A
authors.lastname: Tumanov
authors.forename: Yang-Xin
authors.initials: YX
authors.lastname: Fu
authors.forename: Nir
authors.initials: N
authors.lastname: Hacohen
authors.forename: Ulrich H
authors.initials: UH
authors.lastname: von Andrian
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D057134:Antibodies, Neutralizing / Q000378:metabolism; D000914:Antibodies, Viral / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology*; D007113:Immunity, Innate; D007370:Interferon Type I / Q000096:biosynthesis; D008198:Lymph Nodes / Q000276:immunology; D053361:Lymphotoxin alpha1, beta2 Heterotrimer / Q000378:metabolism; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction / Q000276:immunology; D054243:Vesicular Stomatitis / Q000276:immunology*; D018116:Vesiculovirus / Q000276:immunology / Q000472:pathogenicity
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007370:Interferon Type I; D053361:Lymphotoxin alpha1, beta2 Heterotrimer