MyD88- and Bruton’s Tyrosine Kinase-Mediated Signals Are Essential for T Cell-Independent Pathogen-Specific IgM Responses

摘要: Bacteremia is one of the leading causes death by infectious disease. To understand immune mechanisms required for rapid control bacteremia, we studied Borrelia hermsii , a bacterial pathogen that colonizes blood stream humans and rodents to an extremely high density. A T cell-independent IgM response essential sufficient controlling B. bacteremia. Mice deficient in Bruton’s tyrosine kinase (Btk), despite their known defect BCR signaling, generated -specific resolved suggesting alternative activation or costimulatory pathway remained functional B cells Btk −/− mice. contains putative ligands TLRs, found mice TLR1, TLR2, TLR adaptor MyD88 anti- with delayed kinetics suffered more severe episodes In striking contrast only Btk, both were entirely incapable generating hermsii- specific Ab resolving The cell-dependent model Ag was unaffected × These results suggest specifically promotes signaling that, absence this TLR-mediated stimulation component signal.