title: Toll-like receptor 9 signaling acts on multiple elements of the germinal center to enhance antibody responses.
abstract: Recent studies have demonstrated important roles of nucleic acid-sensing Toll-like receptors (TLRs) in promoting protective antibody responses against several viruses. To dissect how recognition of nucleic acids by TLRs enhances germinal center (GC) responses, mice selectively deleted for myeloid differentiation primary-response protein 88 (MyD88) in B cells or dendritic cells (DCs) were immunized with a haptenated protein antigen bound to a TLR9 ligand. TLR9 signaling in DCs led to greater numbers of follicular helper T (TFH) cells and GC B cells, and accelerated production of broad-affinity antihapten IgG. In addition to modulating GC selection by increasing inducible costimulator (ICOS) expression on TFH cells and reducing the number of follicular regulatory T cells, MyD88-dependent signaling in B cells enhanced GC output by augmenting a class switch to IgG2a, affinity maturation, and the memory antibody response. Thus, attachment of a TLR9 ligand to an oligovalent antigen acted on DCs and B cells to coordinate changes in the T-cell compartment and also promoted B cell-intrinsic effects that ultimately programmed a more potent GC response.
authors: Department of Molecular and Cell Biology, Life Sciences Addition, University of California, Berkeley, CA 94720; and.
authors: Derek C
authors: DC
authors: Rookhuizen
authors: Department of Microbiology and Immunology, University of California, San Francisco, CA 94143 anthony.defranco@ucsf.edu.
authors: Anthony L
authors: AL
authors: DeFranco
mesh_terms: D000818:Animals; D000915:Antibody Affinity / Q000187:drug effects; D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002645:Chickens; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000378:metabolism; D018858:Germinal Center / Q000276:immunology*; D006241:Haptens / Q000494:pharmacology; D007156:Immunologic Memory / Q000187:drug effects; D008024:Ligands; D008213:Lymphocyte Activation / Q000187:drug effects; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D009596:Nitrophenols / Q000494:pharmacology; D010641:Phenotype; D015398:Signal Transduction / Q000276:immunology*; D051217:Toll-Like Receptor 9 / Q000378:metabolism*; D005719:gamma-Globulins / Q000494:pharmacology
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D006241:Haptens; D008024:Ligands; D053594:Myeloid Differentiation Factor 88; D009596:Nitrophenols; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D005719:gamma-Globulins