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Toll-like receptor 4-mediated signaling regulates IL-7-driven proliferation and differentiation of B-cell precursors

Cellular & Molecular Immunology volume 11, pages 132–140 (2014)Cite this article

Abstract

Lipopolysaccharide (LPS) is known to be a potent activator of mature B cells by signaling through Toll-like receptor 4 (TLR4). Its impact on early B-cell development, however, is not well defined. When comparing to C3H/HeN mice, TLR4-mutant C3H/HeJ mice showed an increase in the number of pro-B and pre-B cells in the bone marrow. When cultured in the presence of IL-7, the proliferation of pro-B and large pre-B cells was significantly inhibited by LPS, possibly due to reduced IL-7 receptor-α (IL-7Rα) expression. Meanwhile, the generation of IgM+/IgD+ B cells was greatly enhanced in IL-7 cultures of pro-B and pre-B cells. Consistent with these results, treatment with LPS facilitated the progression of adoptively transferred B220+IgM−IgD− precursors into IgD+ cells. Overall, these data suggest that LPS has a profound influence on early B-cell development, which may contribute to the deregulated B-cell development under physiological and pathological conditions such as bacterial infections.

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Acknowledgements

We thank Xiaoping Qian and Xuewen Pang for excellent technical assistance. We also thank Yanhui Yin and Qing Ge for valuable discussions and critical comments. This work was supported by grants from the National Basic Research Program of China (2011CB946100), National Natural Sciences Foundation of China (30830091 to YZ and 30960357 to RL) and the 111 Project of China (B07001).

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Author notes

  1. Dr Y Zhang, Department of Immunology, Key Laboratory of Medical Immunology of Ministry of Health, Peking University Health Science Center, Beijing, China. E-mail: zhangyu007@hsc.pku.edu.cn

  2. Dr R Li, Department of Microbiology, Faculty of Basic Medical Sciences, Institute of Translational Medicine, Nanchang University, Nanchang, China. E-mail: lirong1973@gmail.com

Authors and Affiliations

  1. Department of Immunology, Key Laboratory of Medical Immunology of Ministry of Health, Peking University Health Science Center, Beijing, China

    Qian Li, Dongmei Han, Wei Wang, Xiuyuan Sun, Jun Zhang & Yu Zhang

  2. Department of Microbiology, Faculty of Basic Medical Sciences, Institute of Translational Medicine, Nanchang University, Nanchang, China

    Xiaoqing Liu & Rong Li

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Li, Q., Han, D., Wang, W. et al. Toll-like receptor 4-mediated signaling regulates IL-7-driven proliferation and differentiation of B-cell precursors. Cell Mol Immunol 11, 132–140 (2014). https://doi.org/10.1038/cmi.2013.55

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