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

摘要: 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 is mediated IgG, we sought the mechanisms that trigger humoral immunity to HPV16 VLP. We find VLP bind murine B lymphocytes thereby inducing activation-induced cytidine deaminase expression Ig class switch recombination cause generation of IgG. also activate production proinflammatory factors IFN-alpha, IL-6, MIP-1alpha, RANTES, KC, up-regulate costimulatory molecules naive cells, increase B1 cell subpopulation. These responses are dependent upon MyD88. Although MyD88(-/-) cells produce only mu transcript after exposure VLP, MyD88(+/+) express alpha, gamma, H chain transcripts. Notably, TLR4 mutant C3H/HeJ mice exhibited significantly reduced VLP-specific IgG1, IgG2a, IgG2b, IgG3 titers vaccination as compared control C3H/HeOuJ mice. directly activated molecule but not Thus induce CD4(+) T independent immune via TLR4- MyD88-dependent signaling.