Impaired granzyme B-producing regulatory B cells in systemic lupus erythematosus. (December 2021)

• Record Type: Journal Article
• Authors: Bai, Mingxin; Xu, Liling; Zhu, Huaqun; Xue, Jimeng; Liu, Tian; Sun, Feng; Yao, Haihong; Zhao, Zhen; Wang, Ziye; Yao, Ranran; Hu, Fanlei; Su, Yin
• Is Part Of: Molecular immunology. Volume 140(2021)
• Page Start: 217
• Page End: 224
• Publication Date: 2021-12
• Subjects: GrB granzyme B -- Bregs regulatory B cells -- SLE systemic lupus erythematosus -- NK cells natural killer cells -- PBMCs peripheral blood mononuclear cells -- SLEDAI systemic lupus erythematosus disease activity index -- HC healthy controls -- PMA phorbol myristate acetate -- BFA brefeldin A -- WBC white blood cells -- RBC red blood cells -- Hb hemoglobin -- PLT platelets -- ESR erythrocyte sedimentation rate -- CRP C-reactive protein -- C3 complement component 3 -- C4 complement component 4 -- AnuA anti-nucleosome antibody -- Anti-dsDNA Ab anti-double strand DNA Antibody -- IgA/G/M immunoglobulin A/G/M; Systemic lupus erythematosus -- B cells -- Granzyme B -- Disturbance; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2021.09.012
• Languages: English
• ISSNs: 0161-5890

Abstract

Highlights: The frequencies of GrB-producing B cells were significantly decreased in SLE patients. GrB-producing B cells were negatively correlated with SLE disease activities and manifestations. GrB-producing B cells were functionally impaired in regulating CD4 + T cell responses in SLE. Abstract: Granzyme B (GrB)-producing B cells are proposed to be a kind of regulatory B cells (Bregs) and have been revealed to be implicated in the pathogenesis of autoimmune diseases. Nevertheless, their role in SLE remains elusive. In this study, the frequencies of GrB-producing Bregs in peripheral blood of heathy control (HC) and systemic lupus erythematosus (SLE) were evaluated by flow cytometry, and their correlation with SLE patient clinical and immunological features were analyzed. The expression of GrB in HC and SLE B cells were also further detected by RT-qPCR analysis and ELISpot. The function of GrB-producing Bregs in HC and SLE patients was further investigated by in vitro CD4 + effector T cells-B cells co-culture assays with GrB blockade. We found that GrB-producing Bregs were significantly decreased in SLE patients and correlated with the clinical and immunological features. Moreover, these cells were functionally impaired under SLE circumstance. The negative correlation between GrB-producing Bregs and CD4 + T cells observed in healthy individuals disappeared in SLE patients. In vitro cell co-culture assay further showed that GrB-producing Bregs from SLE patients failed to suppress the Th1, Th2 and Th17 cell inflammatory responses, partially due to the dampened capacity of down-regulating TCR zeta and inducing T cell apoptosis. Taken together, these results revealed the disturbance of GrB-producing Bregs in SLE that might contribute to the disease initiation and progression.