B Cell–Intrinsic MyD88 Signaling Promotes Initial Cell Proliferation and Differentiation To Enhance the Germinal Center Response to a Virus-like Particle

Journal of Immunology - Tập 200 Số 3 - Trang 937-948 - 2018
Meijie Tian1, Zhaolin Hua1,2, Hong Sheng1, Zhimin Zhang1, Can Liu1, Lin Lin1, Jiaorong Chen1, Wei Zhang3, Xuyu Zhou2,3, Fuping Zhang2,3, Anthony DeFranco4, Baidong Hou1,2
1Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
2University of Chinese Academy of Sciences, Beijing, 100049, China
3‡Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; and
4§Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143

Tóm tắt

Abstract Although TLR signaling in B cells has been implicated in the germinal center (GC) responses during viral infections and autoimmune diseases, the underlying mechanism is unclear. Bacterial phage Qβ-derived virus-like particle (Qβ-VLP) contains TLR ligands, which can enhance Qβ-VLP-induced Ab response, including GC response, through TLR/MyD88 signaling in B cells. In this study, by examining Ag-specific B cell response to Qβ-VLP, we found that lack of B cell MyD88 from the beginning of the immune response led to a more severe defect in the GC scale than abolishing MyD88 at later time points of the immune response. Consistently, B cell–intrinsic MyD88 signaling significantly enhanced the initial proliferation of Ag-specific B cells, which was accompanied with a dramatic increase of plasma cell generation and induction of Bcl-6+ GC B cell precursors. In addition, B cell–intrinsic MyD88 signaling promoted strong T-bet expression independent of IFN-γ and led to the preferential isotype switching to IgG2a/c. Thus, by promoting the initial Ag-specific B cell proliferation and differentiation, B cell–intrinsic MyD88 signaling enhanced both T-independent and T-dependent Ab responses elicited by Qβ-VLP. This finding will provide additional insight into the role of TLR signaling in antiviral immunity, autoimmune diseases, and vaccine design.

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Journal of Immunology

Tập 200 Số 3

937-948

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