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CXCR4 and CXCR5 orchestrate dynamic germinal center reactions and may contribute to the pathogenesis of systemic lupus erythematosus

Cellular & Molecular Immunology volume 16, pages 724–726 (2019)Cite this article

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In a previous publication in Cellular and Molecular Immunology, Zhao et al.1 showed data from patients with treatment-naïve systemic lupus erythematosus (SLE), demonstrating the clinical significance and possible mechanisms of the aberrant expression of the chemokine receptor CXCR4 on lupus B cells. In this commentary, we will discuss the roles of CXCL12-CXCR4 and CXCL13-CXCR5 pairs and related signaling pathways in guiding dynamic germinal center (GC) reactions and B cell selection and describe how their dysregulation may contribute to the pathogenesis of SLE.

B cells play a central role in the pathogenesis of SLE as the precursors of autoantibody-secreting cells, powerful antigen-presenting cells and cytokine producers.2 Although antibody-secreting cells (ASCs) could derive extrafollicularly, GC is believed to be the main site for generating long-lived plasma cells and memory B cells, which are overactivated in SLE and capable of producing pathogenic autoantibodies persistently.3 In GC, B cells are subdued to affinity-driven evolution and selection, followed by clonal expansion or deletion. It remains to be elucidated how these autoreactive B cells could survive clonal deletion in GC and escape into peripheral circulation. Failure of appropriate B cell receptor (BCR) repertoire trimming in GC may originate from imbalanced programming intrinsically, impaired function of helper cells extrinsically and abnormal translocation and immigration associated with intrinsic and extrinsic signals. Numerous studies have addressed the roles of BCRs, toll-like receptors (TLRs) and intracellular signaling pathways, as well as chemokines and their specific receptors, in regulating B cells escape from stringent GC negative selection, subsequent differentiation into plasma cells and their exit into the periphery.3,4,5

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Acknowledgements

This study was supported by grants from the National Natural Science Foundation of China (81788101, 81630044, 81601432, 81771763, 91542000), the Chinese Academy of Medical Science Innovation Fund for Medical Sciences (CIFMS2016-I2M-1-003, 2017-I2M-1-008, 2017-I2M-3-011, 2016-I2M-1-008), and the Natural Science Foundation of Beijing, China (7182129).

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  1. Department of Rheumatology and Clinical Immunology, Clinical Immunology Center, Medical Epigenetics Research Center, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College Hospital, 100730, Beijing, China

    Bing-xuan Wu, Li-dan Zhao & Xuan Zhang

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  1. Bing-xuan Wu
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Correspondence to Li-dan Zhao or Xuan Zhang.

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Wu, Bx., Zhao, Ld. & Zhang, X. CXCR4 and CXCR5 orchestrate dynamic germinal center reactions and may contribute to the pathogenesis of systemic lupus erythematosus. Cell Mol Immunol 16, 724–726 (2019). https://doi.org/10.1038/s41423-019-0244-y

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