The role of B lymphocyte stimulator (BLyS) in systemic lupus erythematosus
Michael P. Cancro, … , David P. D’Cruz, Munther A. Khamashta
Michael P. Cancro, … , David P. D’Cruz, Munther A. Khamashta
Published May 1, 2009
Citation Information: J Clin Invest. 2009;119(5):1066-1073. https://doi.org/10.1172/JCI38010.
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Science in Medicine

The role of B lymphocyte stimulator (BLyS) in systemic lupus erythematosus

Abstract

SLE, a chronic, multisystem autoimmune disorder with a broad range of symptoms, involves defective B cell selection and elimination of self-reactive B cells. B lymphocyte stimulator (BLyS), a soluble ligand of the TNF cytokine family, is a prominent factor in B cell differentiation, homeostasis, and selection. BLyS levels affect survival signals and selective apoptosis of autoantibody-producing B cells. High levels of BLyS may relax B cell selection and contribute to autoantibody production, exacerbating the SLE disease state. This review discusses the mechanism of BLyS action on B cells, its role in SLE, and specific targeting of BLyS in the treatment of SLE.

Authors

Michael P. Cancro, David P. D’Cruz, Munther A. Khamashta

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Figure 1

BLyS and APRIL ligands and receptors.

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BLyS and APRIL ligands and receptors. BLyS is the only ligand for BR3, a...
BLyS is the only ligand for BR3, and both APRIL and BLyS bind to TACI and BCMA. APRIL binds to TACI and BCMA with higher affinity than does BLyS. Intracellular signaling from the ligand binding leads to B cell survival and influences B cell differentiation. These effects involve the activation of transcriptional regulatory factors such as RelA and RelB, which can regulate the expression of antiapoptotic proteins, including Bcl-2, A-1, Bcl-XL, and Mcl-1.