T-helper signals restore B-cell receptor signaling in autoreactive anergic B cells by upregulating CD45 phosphatase activity

• Published in: Journal of allergy and clinical immunology Vol. 138; no. 3; pp. 839 - 851.e8
• Main Authors: Szodoray, Peter, Stanford, Stephanie M., Molberg, Øyvind, Munthe, Ludvig A., Bottini, Nunzio, Nakken, Britt
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2016; Elsevier Limited
• Subjects: Adult; Allergy and Immunology; Antigens; Autoimmune diseases; B-cell anergy; B-Lymphocytes - immunology; Blood & organ donations; break of tolerance; Calcium - metabolism; CD45 phosphatase activity; Cells, Cultured; Clonal Anergy; Disease; Human subjects; Humans; Immunoglobulins; Kinases; Leukocyte Common Antigens - genetics; Leukocyte Common Antigens - immunology; Leukocyte Common Antigens - metabolism; Lupus Erythematosus, Systemic - immunology; Pathogenesis; Phosphatase; Population; Receptors, Antigen, B-Cell - immunology; RNA, Messenger - metabolism; Rodents; Signal Transduction; src-Family Kinases - genetics; Syk Kinase - genetics; systemic lupus erythematosus; T cell receptors; T-cell help; T-Lymphocytes - immunology; Up-Regulation; CD40L; CD45 phosphatase activity; T-cell help; Treg; B-cell anergy; CFSE; BND cells; break of tolerance; SLE; HEL; BCR; pCAP; systemic lupus erythematosus; FITC; APC; ITAM; PE; pErk1/2; Csk; PerCP; Fluorescein isothiocyanate; B-cell receptor; Peridinin-chlorophyll-protein complex; Hen egg lysozyme; Allophycocyanin; Regulatory T; Phosphorylated extracellular signal-regulated kinase 1/2; B-cell population that is naturally autoreactive and tolerized by functional anergy; Phosphorylated coumaryl amino propionic acid; Carboxyfluorescein succinimidyl ester; C-terminal Src kinase; CD40 ligand; Phycoerythrin; Immunoreceptor tyrosine-based activation motif; B ND cells

We recently identified a human B-cell population that is naturally autoreactive and tolerized by functional anergy (BND cells). We sought to identify the molecular mechanism of how anergic autoreactive BND cells escape functional anergy and whether this process is altered in patients with lupus. Iso...