title: TLR9 signaling in B cells determines class switch recombination to IgG2a.
abstract: Although IgG2a is the most potent Ab isotype in the host response to viral and bacterial infections, the regulation of class switch recombination to IgG2a in vivo is not yet well understood. Recognition of pathogen-associated molecular patterns by dendritic cells expressing TLRs, like TLR7, recognizing ssRNA, or TLR9, recognizing DNA rich in nonmethylated CG motifs (CpG), favors induction of Th1 responses. It is generally assumed that these Th1 responses are responsible for the TLR-mediated induction of IgG2a. Using virus-like particles loaded with CpGs, we show here that TLR9 ligands can directly stimulate B cells to undergo isotype switching to IgG2a. Unexpectedly, TLR9 expression in non-B cells did not affect isotype switching in the Ab response against virus-like particles. Thus, TLR9 can regulate isotype switching to IgG2a directly by interacting with B cells rather than indirectly by inducing Th1 responses.
authors.affiliation: Cytos Biotechnology AG, Zurich-Schlieren, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Jegerlehner
authors.forename: Patrik
authors.initials: P
authors.lastname: Maurer
authors.forename: Juliana
authors.initials: J
authors.lastname: Bessa
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Hinton
authors.forename: Manfred
authors.initials: M
authors.lastname: Kopf
authors.forename: Martin F
authors.initials: MF
authors.lastname: Bachmann
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D001424:Bacterial Infections / Q000276:immunology; D018899:CpG Islands / Q000276:immunology; D017578:Immunoglobulin Class Switching / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D008024:Ligands; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D012313:RNA / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology; D051199:Toll-Like Receptor 7 / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000276:immunology*; D014777:Virus Diseases / Q000276:immunology
chemical_list: D007074:Immunoglobulin G; D008024:Ligands; D008562:Membrane Glycoproteins; C477038:Tlr7 protein, mouse; C495370:Tlr9 protein, mouse; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9; D012313:RNA