Increased BCMA expression in lupus marks activated B cells, and BCMA receptor engagement enhances the response to TLR9 stimulation

Abstract

B lymphocyte stimulator (BLyS) and APRoliferation inducing ligand (APRIL) are members of the TNF superfamily that regulate B-cell survival and autoreactivity. To further understand the significance of elevated BLyS and APRIL in systemic lupus erythematosus (SLE), we examined the expression profiles of their receptors (B-cell-activating factor (BAFF)-R, transmembrane activator and calcium modulator and cyclophilin ligand interactor, and B cell maturation antigen (BCMA)) on B-cell subsets in SLE and also investigated the differential expression and function of BCMA in TLR9-induced B-cell activation. While BAFF-R expression on SLE B cells was significantly lower compared to healthy control B cells (p = 0.003), BCMA expression was substantially higher on SLE B cells (p = 0.038), especially on memory cells and plasmablasts. BCMA⁺ cells had higher CD19 and CD86 expression, indicating a greater degree of activation in both healthy and lupus patients. CpG stimulation increased BCMA expression on B cells and induced the proliferation and maturation of BCMA⁺ B cells. A BCMA agonistic antibody also enhanced CpG-induced proliferation, activation, and IgG secretion by B cells in both healthy controls and lupus patients. Furthermore, the agonistic BCMA antibody co-stimulated auto-antibody production by CpG-stimulated lupus B cells in vitro. Signaling through BCMA enhances B cell activation following exposure to TLR9 agonists, and increased expression in SLE may contribute to the production of IgG autoantibodies.

Keywords::

• Systemic lupus erythematosus
• BLyS
• APRIL
• BCMA
• TLR9

Acknowledgments

This study was supported by a grant from ZymoGenetics Inc. and Merck-Serono International, S.A. We thank David Rawlings (University of Washington) for helpful discussion and Jeffrey Ledbetter (University of Washington) for critical review of the manuscript.

Declaration of interest: This study is partly supported by a grant from ZymoGenetics Inc. and Merck-Serono International, S.A.