Figure 3.

B-cell implications in the pathogenic processes involved in systemic sclerosis. (A) Organ infiltration: B-cell infiltrates are present in various organs involved in SSc. These infiltrates combine B and T cells, plasma cells, dendritic cells and macrophages, underlying their interactions. (B) B-cell subpopulations: B-cells express at their surfaces multiple molecules involved in activation or surviving pathway, as well as decreased levels of inhibitors coreceptors. B-cells also express co-receptors required for interaction with T cell. (C) B-cell intracellular signaling, genomic, transcriptomic and proteomic data argue a B-cell signature in SSc. (D) Autoantibodies. Several autoantibodies have demonstrated their involvement in cell activation, apoptosis induction, proinflammatory and profibrotic processes. (E, F) Cell to cell interactions and cytokines synthesis: B-cells interact with various immune cells, fibroblast and endothelial cell through direct (solid line) and indirect contact (i.e., cytokines and antibodies; dotted line). All participate in profibrotic, proinflammatory processes, vascular remodeling and immune dysregulations. Abs, antibodies; AECA, anti-endothelial cell Abs; AFA, anti-fibroblast Abs; anti-VSMC Abs, anti-vascular smooth muscle cell Abs; BAFF-R, calcium-modulator and cyclophilin ligand-interactor and BAFF receptor; BCMA, B-cell survival membrane receptors: B-cell maturation protein; BCR, B-cell receptor; CD, cluster of differentiation; DCs, dendritic cells; HLA-II, human leukocyte antigen class II; ICOS, inducible T-cell costimulatory; IL, interleukin; IL6-R, IL6 receptorPD-1/PD-L2: programmed death/programmed death ligand immune checkpoint; pDCs, plasmacytoid dendritic cells; TACI, trans-membrane activator.