Stimulation with FITC-labeled antigens confers B cells with regulatory properties

• Published in: Cellular immunology 2020-09, Vol.355, p.104151-104151, Article 104151
• Main Authors: Planchais, Cyril, Rayes, Julie, Delignat, Sandrine, Pashova, Shina, Varthaman, Aditi, Pashov, Anastas, Bayry, Jagadeesh, Kaveri, Srinivas V., Dimitrov, Jordan D., Lacroix-Desmazes, Sebastien
• Format: Article
• Language: English
• Subjects: Animals; B-Lymphocyte Subsets - immunology; B-Lymphocytes - drug effects; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; B-Lymphocytes, Regulatory - immunology; B-Lymphocytes, Regulatory - metabolism; CD4-Positive T-Lymphocytes - immunology; Cell Differentiation - immunology; Cytokines - metabolism; Encephalomyelitis, Autoimmune, Experimental - immunology; Experimental autoimmune encephalitis; Female; Fluorescein - metabolism; Fluorescein - pharmacology; Fluorescein-5-isothiocyanate - chemistry; Fluorescein-5-isothiocyanate - metabolism; Fluorescein-5-isothiocyanate - pharmacology; IL-10; Immuno-modulatory B cells; Immunology; Interleukin-10 - immunology; Interleukin-10 - metabolism; Interleukins - immunology; Interleukins - metabolism; Life Sciences; Lymphocyte Activation - immunology; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Myelin-Oligodendrocyte Glycoprotein - immunology; T-Lymphocytes, Regulatory - immunology; Transforming Growth Factor beta - metabolism
• ISSN: 0008-8749; 1090-2163
• DOI: 10.1016/j.cellimm.2020.104151

•Fluorescein isothiocyanate (FITC) binds to ~20% of splenic B cells from naïve mice.•Binding of antigen-coupled FITC to B cells induces IL-10 production and antigen endocytosis.•OVA-FITC loaded B cells polarizes OTII T cells towards a Tr1/Th2 phenotype.•MOG-FITC-loaded B cells protects mice from EAE upon adoptive transfer. B cells with regulatory properties (Bregs) were identified in human and in mice among different B-cell subsets. Their regulatory properties rely mainly on the production of anti-inflammatory cytokines, in particular IL10, IL-35 and TGFβ, and were extensively studied in mouse models of autoimmune and inflammatory diseases. However, the exact nature of the stimulatory signals conferring regulatory properties to B cells is still not clear. We serendipitously observed that fluorescein isothiocyanate (FITC) binds to a significant proportion of naïve mouse B cells. Binding of FITC to the B-cell surface implicated at least in part the B-cell receptor. It triggered IL-10 production and allowed the endocytosis of FITC-coupled antigens followed by their presentation to CD4+ T cells. In particular, B cells incubated with FITC-OVA polarized OTII T cells towards a Tr1/Th2 phenotype in vitro. Further, the adoptive transfer of B cells incubated with FITC-labeled myelin oligodendrocyte glycoprotein peptide protected mice from experimental autoimmune encephalomyelitis, a T-cell-dependent autoimmune model. Together, the data show that FITC-stimulated B cells polarize immune responses towards Tr1/Th2 and acquire immuno-modulatory properties.