Autoantibody-producing RP105− B cells, from patients with systemic lupus erythematosus, showed more preferential expression of BCMA compared with BAFF-R than normal subjects

• Published in: Rheumatology (Oxford, England) England), 2010-04, Vol.49 (4), p.662-670
• Main Authors: Koarada, Syuichi, Tada, Yoshifumi, Sohma, Yoshiaki, Haruta, Yoshio, Suematsu, Rie, Mitamura, Mio, Inoue, Hisako, Ehara, Hiromi, Tokoro, Yusuke, Ohta, Akihide, Nagasawa, Kohei
• Format: Article
• Language: English
• Subjects: A proliferation-inducing ligand; Adolescent; Adult; Aged; Autoantibodies - immunology; Autoantibody; B cells; B-cell activating factor; B-cell activating factor receptor; B-Cell Activation Factor Receptor - genetics; B-Cell Activation Factor Receptor - immunology; B-cell maturation antigen; B-Cell Maturation Antigen - genetics; B-Cell Maturation Antigen - immunology; Case-Control Studies; CD40L; Female; Flow Cytometry; Humans; Lupus Erythematosus, Systemic - genetics; Lupus Erythematosus, Systemic - immunology; Male; Middle Aged; Polymerase Chain Reaction; RP105 (CD180); SLE; Transmembrane activator and cyclophilin ligand interactor; Young Adult
• ISSN: 1462-0324; 1462-0332
• DOI: 10.1093/rheumatology/kep437

Objective. B cells lacking RP105 produce autoantibodies in patients with SLE. Expression of B-cell activating factor (BAFF) binding receptors (BBRs) and survival of RP105− B cells from SLE patients were examined. Methods. Detection of difference of gene expression between RP105− and RP105+ B cells was done by DNA microarrays. Surface expression was confirmed by flow cytometry. The contribution of BAFF, a proliferation-inducing ligand (APRIL) and monomers/trimers of sCD40L to survival of RP105− and RP105+ B cells was examined. Results. Gene expression of B-cell maturation antigen (BCMA) was different among BBRs in RP105− and RP105+ B cells in SLE. Preferential expression of BCMA on RP105− B cells was confirmed compared with RP105+ B cells by flow cytometry, although BAFF receptor (BAFF-R) expression on RP105− B cells was significantly lower. Additionally, relative ratios of BCMA/BAFF-R expression on RP105− B cells were increased significantly in SLE patients compared with normal subjects. Stimulation by sCD40L decreased the number of surviving RP105− and RP105+ B cells in vitro. RP105+ B cells were not rescued from sCD40L-induced cell death by BAFF and/or APRIL. In contrast, either BAFF or APRIL maintained the survival of RP105− B cells due to avoidance of cell death. Activated RP105− B cells reduced BAFF-R and increased BCMA levels. Conclusions. RP105− B cells from SLE patients showed more preferential expression of BCMA compared with BAFF-R than normal subjects, and were possibly regulated by BAFF/APRIL. Our results provide a new insight of BCMA and their ligands in B cells from SLE patients.