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CX3CR1 positively regulates BCR signaling coupled with cell metabolism via negatively controlling actin remodeling

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A Correction to this article was published on 13 May 2020

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Abstract

As an important chemokine receptor, the role of CX3CR1 has been studied extensively on the migration of lymphocytes including T and B cells. Although CX3CR1+ B cells have immune suppressor properties, little is known about its role on the regulation of BCR signaling and B cell differentiation as well as the underlying molecular mechanism. We have used CX3CR1 KO mice to study the effect of CX3CR1 deficiency on BCR signaling and B cell differentiation. Interestingly, we found that proximal BCR signaling, such as the activation of CD19, BTK and SHIP was reduced in CX3CR1 KO B cells upon antigenic stimulation. However, the activation of mTORC signaling was enhanced. Mechanistically, we found that the reduced BCR signaling in CX3CR1 KO B cells was due to reduced BCR clustering, which is caused by the enhanced actin accumulation by the plasma membrane via increased activation of WASP. This caused an increased differentiation of MZ B cells in CX3CR1 KO mice and an enhanced generation of plasma cells (PC) and antibodies. Our study shows that CX3CR1 regulates BCR signaling via actin remodeling and affects B cell differentiation and the humoral immune response.

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  • 13 May 2020

    In the original published version of the article, the red squares in the figures which indicated the corrections.

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Acknowledgements

This study was supported by the Natural Science Foundation of China (81861138002, 81722002 and 31970839) and the start-up funding from Huazhong University of Science and Technology.

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Author notes

  1. Na Li and Panpan Jiang contributed equally to this work.

Authors and Affiliations

  1. Clinical Molecular Immunology Center, Department of Immunology, School of Medicine, Yangtze University, Jingzhou, 434023, China

    Na Li, Qiuyue Chen & Quan Gong

  2. Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Panpan Jiang, Yukai Jing, Lu Yang, Danqing Kang, Ju Liu, Jiang Chang & Chaohong Liu

  3. Chongqing Key Laboratory of Child Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing, 400016, China

    Anwei Chen

  4. BIOSS Centre for Biological Signalling Studies, Albert Ludwigs University of Freiburg, 79104, Freiburg Im Breisgau, Baden-Württemberg, Germany

    Julia Jellusova

  5. Department of Intracellular Pathogens, National Institute of Allergy and Infectious Diseases, Bethesda, MT, 59840, USA

    Heather Miller

  6. Department of Microbiology Tumor and Cell Biology, KarolinskaInstitutet, Stockholm, 17177, Sweden

    Lisa Westerberg

  7. The Center for Biomedical Research, Key Laboratory of Organ Transplantation, Ministry of Education and Chinese Academy of Medical Sciences, NHC Key Laboratory of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Xi Luo & Cong-Yi Wang

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  1. Na Li
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Contributions

NL and PJ drafted the initial manuscript. CL designed the research, reviewed and revised the manuscript. AC performed the TRIFm experiments, XL and NL performed Seahorse experiments. NL and YJ performed the confocal experiments. NL, YJ, LY, PJ, DK, JL, JC, QC carried out the flow cytometry assay, ELISA, and Western blotting. NL analyzed the data and generated figures. JJ, HM, LW, CW, QG assisted with the manuscript. All authors approved the final manuscript as submitted and agreed to be accountable for all aspects of the work.

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Correspondence to Quan Gong or Chaohong Liu.

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Li, N., Jiang, P., Chen, A. et al. CX3CR1 positively regulates BCR signaling coupled with cell metabolism via negatively controlling actin remodeling. Cell. Mol. Life Sci. 77, 4379–4395 (2020). https://doi.org/10.1007/s00018-019-03416-7

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