title: Influenza virus infection causes global respiratory tract B cell response modulation via innate immune signals.
abstract: Induction of primary B cell responses requires the presence of Ag and costimulatory signals by T cells. Innate signals further enhance B cell activation. The precise nature and kinetics of such innate immune signals and their functional effects are unknown. This study demonstrates that influenza virus-induced type I IFN is the main innate stimulus affecting local B cells within 48 h of infection. It alters the transcriptional profile of B cells and selectively traps them in the regional lymph nodes, presumably via up-regulation of CD69. Somewhat paradoxically, innate B cell stimulation inhibited the ability of regional lymph node B cells to clonally expand following BCR-mediated stimulation. This inhibition was due to IFNR-signaling independent B cell intrinsic, as well as IFNR-dependent B cell extrinsic, regulation induced following influenza infection. IFNR-mediated signals also reduced B cell migration to various chemotactic agents. Consistent with the lack of responsiveness to CCR7 ligands, unaltered or reduced expression of MHC class II and genes associated with MHC class II Ag processing/presentation and CD40, B cells were unable to induce proliferation of naive CD4 T cells. Instead, they showed increased expression of a subset of nonclassical MHC molecules that facilitate interaction with gammadelta T cells and NK T cells. We conclude that type I IFN is the main "third" B cell signal following influenza infection causing early trapping of B cells in regional lymph nodes and, at a time when cognate T cell help is rare, enhancing their propensity to interact with innate immune cells for noncognate stimulation.
authors.affiliation: Center for Comparative Medicine and.
authors.forename: W L William
authors.initials: WL
authors.lastname: Chang
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Coro
authors.forename: Friederike C
authors.initials: FC
authors.lastname: Rau
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Xiao
authors.forename: David J
authors.initials: DJ
authors.lastname: Erle
authors.forename: Nicole
authors.initials: N
authors.lastname: Baumgarth
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D007113:Immunity, Innate; D007370:Interferon Type I / Q000502:physiology; D007694:Killer Cells, Natural / Q000276:immunology; D008198:Lymph Nodes; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009975:Orthomyxoviridae; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology; D012137:Respiratory System / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
chemical_list: D007370:Interferon Type I; D016692:Receptors, Antigen, T-Cell, gamma-delta