Toll-like receptor 9 signaling antagonizes antigen-specific B cell-helper T cell interactions
JOURNAL OF IMMUNOLOGY(2017)
Abstract
Abstract Key events in T cell-dependent antibody responses are dependent on the ability of B cells to capture antigen and process and present it to follicular helper T cells. Despite its importance, little is known about the regulation of this critical B cell function. Here we focus on the impact of signaling through the innate immune receptor, Toll like receptor 9 (TLR9), on the outcome of a B cell’s encounter with antigen. We show that although TLR9 signaling induced B cell proliferation, and secretion of cytokines and IgM, it blocked the ability of antigen-specific B cells to capture, process and present antigen. In the presence of the TLR9 agonist, CpG, B cells were less able to form synapses with antigen-containing membranes and to pull antigen from them. CpG also diminished the ability of the BCR to traffick antigen within the cell to antigen processing compartments resulting in fewer MHC-peptide complexes on the B cell surface. TLR signaling also antagonized the BCR-induced increases in the expression of both MHC class II and important co-receptors, including CD86, resulting in a decrease in the duration of antigen-specific B cell-T helper cell interaction and the inability of B cells to activate antigen-specific T cells. Chimeric mice that contained either wild type B cells or B cells deficient in TLR signaling when immunized with antigen adjuvanted with CpG showed that the loss of the B cells’ ability to respond to CpG resulted in lower antigen-specific IgM responses but enhanced high affinity antigen-specific IgG responses. Thus, B cell intrinsic TLR9 signaling may ensure rapid B cell expansion and antibody secretion at the expense of the ability of B cells to engage in germinal center events that are highly dependent antigen capture and presentation.
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