Bmi1 maintains the self-replenishing ability of B-1a cells in postnatal mice. (HEM1P.230)

Abstract

Abstract B-1a cells are innate immune cells that reside in the peritoneal cavity. We have recently reported that some B-1 cells originate from hemogenic endothelial cells in the early mouse embryo, and are independent of HSC-derived hematopoiesis. B-1a cells are also considered to possess self-replenishing capacity. The mechanisms that permit B-1a cells to undergo self-replenishment in vivo independent of HSCs remain unclear. Bmi1 is a polycomb group protein that is known to be critical for self-renewal of adult BM HSCs. In Bmi1-/- postnatal BM, the number of HSCs was markedly reduced and long-term reconstituting ability was lost. We hypothesized that Bmi1 is also critical for B-1a cell self-replenishment ability. Bmi1 mRNA expression was higher in B-1a cells than other lymphoid subsets in adult wild type mice. In Bmi1-/- mice, absolute cell numbers in the spleen, BM, and peritoneal cavity were decreased but the percentage of each mature lymphoid population was not altered except for B-1a cells. The percentage of peritoneal B-1a cells was 4-7 fold less than wild type. Bmi1-/- B-1a cells displayed impaired self-replenishing ability upon transplantation into the peritoneal cavity of recipient mice. Ink4a-Arf is one of the known target genes of Bmi1, and its expression is increased in Bmi1-/- HSCs and B-1a cells. The percentage and numbers of B-1a cells were restored in Ink4a-/-Arf-/-Bmi1-/- mice. These data suggest that Bmi1 maintains the self-replenishing ability of B-1a cells.