Figure 1.

Linear differentiation model of B10 cell development in vivo in mice and humans. B10 cells originate from a progenitor population (B10_PRO). In mice, B10_PRO cells are found in the CD1d⁻CD5⁻ adult blood and lymph node B cell subsets and within the CD1d⁻CD5⁺ neonatal spleen and adult peritoneal cavity B cell subsets. CD40 stimulation induces B10_PRO cells to become competent for IL-10 expression, while lipopolysaccharide (LPS) induces B10_PRO cells to become competent for IL-10 expression and induces B10 cells to produce and secrete IL-10. CD1d^hiCD5⁺ IL-10-competent B10 cells in the adult spleen are induced to express IL-10 following stimulation with phorbol esters (phorbol-12-myristate-13-acetate (PMA)) and ionomycin or LPS plus PMA and ionomycin for 5 hours. Following a transient period of IL-10 expression, a small subset of B10 cells can differentiate into antibody-secreting plasma cells (PC). B10 cells also possibly differentiate into memory B10 cells (B10_M). B10 cell development in humans appears to follow the differentiation scheme observed in mice. B10 cells and B10_PRO cells have been identified in human newborn and adult blood. B10+B10_PRO cells in adult human blood express CD27 and CD24. Whether human B10 cells further differentiate into PCs or B10_M remains to be determined. Solid arrows, known associations; dashed arrows, speculated associations. MHC-II, major histocompatibility complex class II.