B Cells in Primary Membranous Nephropathy: Escape from Immune Tolerance and Implications for Patient Management

• Published in: International journal of molecular sciences 2021-12, Vol.22 (24), p.13560
• Main Authors: So, Benjamin Y F, Yap, Desmond Y H, Chan, Tak Mao
• Format: Article
• Language: English
• Subjects: Animals; Antigens; Apoptosis; Autoantibodies; B cells; B-Lymphocytes - drug effects; B-Lymphocytes - immunology; B-Lymphocytes - pathology; Bone marrow; Cytokines; Cytokines - analysis; Cytokines - immunology; Disease Management; Enzymes; Glomerulonephritis, Membranous - immunology; Glomerulonephritis, Membranous - pathology; Glomerulonephritis, Membranous - therapy; Health services; Homeostasis; Humans; immune tolerance; Immune Tolerance - drug effects; Immunological tolerance; Immunopathogenesis; Immunosuppressive Agents - therapeutic use; Kidney diseases; Kinases; Lymphocytes; Lymphocytes B; Membranous nephropathy; Molecular Targeted Therapy; Monitoring; Monoclonal antibodies; Nephropathy; Nephrotic syndrome; Patients; primary membranous nephropathy; Review; Signal transduction; Somatic hypermutation; Telemedicine
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms222413560

Membranous nephropathy (MN) is an important cause of nephrotic syndrome and chronic kidney disease (CKD) in adults. The pathogenic significance of B cells in MN is increasingly recognized, especially following the discovery of various autoantibodies that target specific podocytic antigens and the promising treatment responses seen with B cell depleting therapies. The presence of autoreactive B cells and autoantibodies that bind to antigens on podocyte surfaces are characteristic features of MN, and are the result of breaches in central and peripheral tolerance of B lymphocytes. These perturbations in B cell tolerance include altered B lymphocyte subsets, dysregulation of genes that govern immunoglobulin production, aberrant somatic hypermutation and co-stimulatory signalling, abnormal expression of B cell-related cytokines, and increased B cell infiltrates and organized tertiary lymphoid structures within the kidneys. An understanding of the role of B cell tolerance and homeostasis may have important implications for patient management in MN, as conventional immunosuppressive treatments and novel B cell-targeted therapies show distinct effects on proliferation, differentiation and reconstitution in different B cell subsets. Circulating B lymphocytes and related cytokines may serve as potential biomarkers for treatment selection, monitoring of therapeutic response and prediction of disease relapse. These recent advances in the understanding of B cell tolerance in MN have provided greater insight into its immunopathogenesis and potential novel strategies for disease monitoring and treatment.