Toll-like receptor 9 signaling acts on multiple elements of the germinal center to enhance antibody responses

作者：Rookhuizen Derek C; DeFranco Anthony L^*

来源：Proceedings of the National Academy of Sciences, 2014, 111(31): E3224-E3233.

DOI：10.1073/pnas.1323985111

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 (T-FH) 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 T-FH 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.

• 出版日期2014-8-5