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 2

B cell differentiation and activation and BLyS receptor expression.

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B cell differentiation and activation and BLyS receptor expression. (A) ...
(A) B cell development and activation. B cells originate and complete initial phases of differentiation and maturation in the bone marrow. Immature B cells exit the bone marrow and move to the circulation as TR B cells, then complete maturation in the spleen. If activated by antigen and T cell help, these mature preimmune B cells will proliferate and form germinal centers, culminating in the generation of memory and plasma cells that make high-affinity, isotype-switched antibodies. (B) B cell developmental stages and BLyS receptor expression. BLyS dependence ensues at the TR developmental stages, at which BR3 and TACI are first expressed. These receptors remain expressed among all preimmune populations. After antigen-driven activation, BLyS receptor expression shifts to predominantly TACI and/or BCMA expression among memory and long-lived plasma cells (the latter of which permanently reside in bone marrow).