Aberrant B Cell Signaling in Autoimmune Diseases

Odilia B.J. Corneth, Stefan F.H. Neys, Rudi W. Hendriks*

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

1 Citation (Scopus)
4 Downloads (Pure)

Abstract

Aberrant B cell signaling plays a critical in role in various systemic and organ-specific autoimmune diseases. This is supported by genetic evidence by many functional studies in B cells from patients or specific animal models and by the observed efficacy of small-molecule inhibitors. In this review, we first discuss key signal transduction pathways downstream of the B cell receptor (BCR) that ensure that autoreactive B cells are removed from the repertoire or functionally silenced. We provide an overview of aberrant BCR signaling that is associated with inappropriate B cell repertoire selection and activation or survival of peripheral B cell populations and plasma cells, finally leading to autoantibody formation. Next to BCR signaling, abnormalities in other signal transduction pathways have been implicated in autoimmune disease. These include reduced activity of several phosphates that are downstream of co-inhibitory receptors on B cells and increased levels of BAFF and APRIL, which support survival of B cells and plasma cells. Importantly, pathogenic synergy of the BCR and Toll-like receptors (TLR), which can be activated by endogenous ligands, such as self-nucleic acids, has been shown to enhance autoimmunity. Finally, we will briefly discuss therapeutic strategies for autoimmune disease based on interfering with signal transduction in B cells.

Original languageEnglish
Article number3391
JournalCells
Volume11
Issue number21
DOIs
Publication statusPublished - 27 Oct 2022

Bibliographical note

Funding Information:
This project was partly supported by grants from the Target2B Consortium, The Dutch Arthritis Foundation (grant no. 19-1-201), and Erasmus MC MRace.

Publisher Copyright:
© 2022 by the authors.

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