Increased BCMA expression in lupus marks activated B cells, and BCMA receptor engagement enhances the response to TLR9 stimulation.
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.
Division of Rheumatology, University of Washington, Seattle, WA 98195, USA.
Jinoh
J
Kim
Jane A
JA
Gross
Stacey R
SR
Dillon
Jun-Ki
JK
Min
Keith B
KB
Elkon
D001323:Autoantibodies / Q000096:biosynthesis / Q000276:immunology; D053264:B-Cell Activating Factor / Q000378:metabolism; D053265:B-Cell Activation Factor Receptor / Q000378:metabolism; D053301:B-Cell Maturation Antigen / Q000235:genetics / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D051217:Toll-Like Receptor 9 / Q000276:immunology / Q000378:metabolism*; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000378:metabolism; D015854:Up-Regulation
D001323:Autoantibodies; D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D053301:B-Cell Maturation Antigen; D007074:Immunoglobulin G; C495371:TLR9 protein, human; C435926:TNFRSF13C protein, human; C086966:TNFRSF17 protein, human; C505719:TNFSF13B protein, human; D051217:Toll-Like Receptor 9; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13