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Review
B-cell depletion in autoimmune diseases
  1. Georg Schett1,2,
  2. György Nagy3,4,5,
  3. Gerhard Krönke1,2,6,
  4. Dirk Mielenz7
  1. 1Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-Universität Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany
  2. 2Deutsches Zentrum Immuntherapie, Friedrich-Alexander-Universität Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany
  3. 3Division of Rheumatology and Clinical Immunology, Department of Internal Medicine and Oncology, Semmelweis University, Budapest, Hungary, Budapest, Hungary
  4. 4Heart and Vascular Center, Semmelweis University, Budapest, Hungary
  5. 5Hospital of the Hospitaller Order of Saint John of God, Budapest, Hungary
  6. 6Department of Rheumatology, Charite, Berlin, Germany
  7. 7Division of Molecular Immunology, Department of Internal Medicine 3, Friedrich-Alexander-Universität Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Bayern, Germany
  1. Correspondence to Professor Georg Schett, Department of Internal Medicine 3-Rheumatology and Immunology, Universitätsklinikum Erlangen, Erlangen, Germany; georg.schett{at}uk-erlangen.de

Abstract

B cells have a pivotal function in the pathogenesis of autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis and systemic lupus erythematosus. In autoimmune disease, B cells orchestrate antigen presentation, cytokine production and autoantibody production, the latter via their differentiation into antibody-secreting plasmablasts and plasma cells. This article addresses the current therapeutic strategies to deplete B cells in order to ameliorate or potentially even cure autoimmune disease. It addresses the main target antigens in the B-cell lineage that are used for therapeutic approaches. Furthermore, it summarises the current evidence for successful treatment of autoimmune disease with monoclonal antibodies targeting B cells and the limitations and challenges of these approaches. Finally, the concept of deep B-cell depletion and immunological reset by chimeric antigen receptor T cells is discussed, as well as the lessons from this approach for better understanding the role of B cells in autoimmune disease.

  • B-Lymphocytes
  • Autoimmune Diseases
  • Therapeutics

https://doi.org/10.1136/ard-2024-225727

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    Footnotes

    • Handling editor Josef S Smolen

    • Correction notice This article has been corrected since it published Online First. The order of authors has been corrected.

    • Contributors All authors contributed to the manuscript.

    • Funding The work of GS is supported by the Deutsche Forschungsgemeinschaft (DFG) through the Leibniz Award, the research group PANDORA FOR2886 and the CRC1483 (EmpkinS) and CRC1181. Further funding has been obtained from the Bundesministerium für Bildung und Forschung (BMBF) through the Mascara project and the European Union (ERC Synergy grant 4D Nanoscope) and the IMI-funded project RTCure. GN is supported by the National Research, Development and Innovation Office Fund in Hungary (2020-2.1.1-ED-2022-00198), the Thematic Excellence Program (Tématerületi Kiválósági Program, TKP2021-EGA-29) of the Ministry for Innovation and Technology in Hungary, OTKA Grant (K 131479). DM is supported by the DFG (FOR2886, Mi939/6-1, GK2599).

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.