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B Cell Aberrance in Lupus: the Ringleader and the Solution

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Abstract

Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease with high heterogeneity but the common characterization of numerous autoantibodies and systemic inflammation which lead to the damage of multiple organs. Aberrance of B cells plays a pivotal role in the immunopathogenesis of SLE via both antibody-dependent and antibody-independent manners. Escape of autoreactive B cells from the central and peripheral tolerance checkpoints, over-activation of B cells and their excessive cytokines release which drive T cells and dendritic cells stimulation, and dysregulated surface molecules, as well as intracellular signal pathways involved in B cell biology, are all contributing to B cell aberrance and participating in the pathogenesis of SLE. Based on that rationale, targeting aberrance of B cells and relevant molecules and pathways is expected to be a promising strategy for lupus control. Multiple approaches targeting B cells through different mechanisms have been attempted, including B-cell depletion via monoclonal antibodies against B-cell-specific molecules, blockade of B-cell survival and activation factors, suppressing T-B crosstalk by interrupting costimulatory molecules and inhibiting intracellular activation signaling cascade by targeting pathway molecules in B cells. Though most attempts ended in failure, the efficacy of B-cell targeting has been encouraged by the FDA approval of belimumab that blocks B cell-activating factor (BAFF) and the recommended use of anti-CD20 as a remedial therapy in refractory lupus. Still, quantities of clinical trials targeting B cells or relevant molecules are ongoing and some of them have displayed promising preliminary results. Additionally, advances in multi-omics studies help deepen our understandings of B cell biology in lupus and may promote the discovery of novel potential therapeutic targets. The combination of real-world data with basic research achievements may pave the road to conquering lupus.

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Funding

This study was supported by grants from the National Natural Science Foundation of China (81788101, 81630044, 81771763), Chinese Academy of Medical Science Innovation Fund for Medical Sciences (CIFMS2017-12M-1-008, 2016-12M-1-003, 2017-I2M-3-011, 2016-12M-1-008), Beijing Capital Health Development Fund (2020-2-4019), and Grant from Medical Epigenetics Research Center, Chinese Academy of Medical Sciences (2017PT31035).

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  1. Department of Rheumatology and Clinical Immunology, The Ministry of Education Key Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing , 100730, China

    YuXue Nie & Lidan Zhao

  2. Clinical Immunology Centre, Medical Epigenetics Research Centre, The Ministry of Education Key Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China

    YuXue Nie & Xuan Zhang

  3. State Key Laboratory of Difficult, Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100730, China

    YuXue Nie & Xuan Zhang

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  1. YuXue Nie
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  2. Lidan Zhao
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Correspondence to Lidan Zhao or Xuan Zhang.

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Nie, Y., Zhao, L. & Zhang, X. B Cell Aberrance in Lupus: the Ringleader and the Solution. Clinic Rev Allerg Immunol 62, 301–323 (2022). https://doi.org/10.1007/s12016-020-08820-7

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