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Figure 2 | Arthritis Research & Therapy

Figure 2

From: IL-10-producing regulatory B cells (B10 cells) in autoimmune disease

Figure 2

B10 cell regulatory effects in autoimmune disease. In this model, unidentifiedautoantigens (auto-Ags) drive early development of B10PRO cells. Following exposure toCD40 ligation and/or Toll-like receptor (TLR) ligands (lipopolysaccharide (LPS), CpG), B10PROcells mature into B10 cells that can actively secrete IL-10 and regulate both innate andadaptive immune responses. IL-21R signaling along with major histocompatibility complex class II(MHC-II) and CD40 cognate interactions with CD4+ T cells, although not needed for B10cell development, are necessary for B10 cell effector functions and result in antigen-specificresponses. B10 cells regulate macrophage function by decreasing their activation, phagocytosis andcytokine and nitric oxide (NO) production. In antigen-presenting cells (APCs), B10-cell-negativeregulation of antigen presentation, expression of co-stimulatory molecules (such as CD86) andproinflammatory cytokine production limits T cell activation. In CD4+ T helper(TH) cells, B10 cells skew responses towards a TH2 phenotype and away fromTH1 and TH17 responses. The negative regulatory effects of B10 cells therebylimit inflammatory responses and subsequent tissue damage. Arrows with solid outline, knownassociations; arrows with dashed outline, speculated associations.

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