B lymphocyte activation by human papillomavirus-like particles directly induces Ig class switch recombination via TLR4-MyD88

Rongcun Yang, Francisco Martinez Murillo, Michael J. Delannoy, R. Lee Blosser, William H. Yutzy IV, Satoshi Uematsu, Kiyoshi Takeda, Shizuo Akira, Raphael P. Viscidi, Richard B.S. Roden

Research output: Contribution to journalArticle

Abstract

Vaccination with human papillomavirus type 16 (HPV16) L1 virus-like particles (VLP) induces both high titer neutralizing IgG and protective immunity. Because protection from experimental infection by papillomavirus is mediated by neutralizing IgG, we sought the mechanisms that trigger humoral immunity to HPV16 L1 VLP. We find that HPV16 L1 VLP bind to murine B lymphocytes thereby inducing activation-induced cytidine deaminase expression and Ig class switch recombination to cause the generation of IgG. HPV16 L1 VLP also activate production of proinflammatory factors EFN-α, IL-6, MIP-1α, RANTES, and KC, up-regulate the expression of costimulatory molecules by naive B cells, and increase the B1 B cell subpopulation. These B cell responses to HPV16 L1 VLP are dependent upon MyD88. Although MyD88-/- B cells produce only μ transcript after exposure to HPV16 L1 VLP, MyD88+/+ B cells express α, γ, and μ Ig H chain and activation-induced cytidine deaminase transcripts. Notably, TLR4 mutant C3H/HeJ mice exhibited significantly reduced HPV16 VLP-specific IgG1, IgG1a, IgG2b, and IgG3 titers after vaccination as compared with the control C3H/HeOuJ mice. HPV16 L1 VLP directly activated class switch recombination and costimulatory molecule expression by B cells of C3H/HeOuJ mice but not C3H/HeJ mice. Thus HPV16 L1 VLP directly activate B cells to induce CD4+ T cell independent humoral immune responses via TLR4- and MyD88-dependent signaling.

Original languageEnglish (US)
Pages (from-to)7912-7919
Number of pages8
JournalJournal of Immunology
Volume174
Issue number12
DOIs
StatePublished - Jun 15 2005

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'B lymphocyte activation by human papillomavirus-like particles directly induces Ig class switch recombination via TLR4-MyD88'. Together they form a unique fingerprint.

  • Cite this