Influenza virus infection causes global respiratory tract B cell response modulation via innate immune signals

W. L William Chang, Elizabeth S. Coro, Friederike C. Rau, Yuanyuan Xiao, David J. Erle, Nicole Baumgarth

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

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 elects are unknown. This study demonstrates that influenza virus-induced type 1 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 γδT cells and NK T cells. We conclude that type 1 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.

Original languageEnglish (US)
Pages (from-to)1457-1467
Number of pages11
JournalJournal of Immunology
Volume178
Issue number3
StatePublished - Feb 1 2007

ASJC Scopus subject areas

  • Immunology

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