Figure 2.

B10 cell regulatory effects in autoimmune disease. In this model, unidentified autoantigens (auto-Ags) drive early development of B10_PRO cells. Following exposure to CD40 ligation and/or Toll-like receptor (TLR) ligands (lipopolysaccharide (LPS), CpG), B10_PRO cells mature into B10 cells that can actively secrete IL-10 and regulate both innate and adaptive 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 B10 cell development, are necessary for B10 cell effector functions and result in antigen-specific responses. B10 cells regulate macrophage function by decreasing their activation, phagocytosis and cytokine and nitric oxide (NO) production. In antigen-presenting cells (APCs), B10-cell-negative regulation of antigen presentation, expression of co-stimulatory molecules (such as CD86) and proinflammatory cytokine production limits T cell activation. In CD4⁺ T helper (T_H) cells, B10 cells skew responses towards a T_H2 phenotype and away from T_H1 and T_H17 responses. The negative regulatory effects of B10 cells thereby limit inflammatory responses and subsequent tissue damage. Arrows with solid outline, known associations; arrows with dashed outline, speculated associations.