BCAP is a negative regulator of myeloid cell development (HEM5P.225)

Abstract

Abstract B cell adaptor for PI3-kinase (BCAP) is a signaling adaptor protein expressed in hematopoietic cells, including myeloid cells. Here we examined the role of BCAP in myeloid cell homeostasis and development. We found an increased number of monocytes in the bone marrow of BCAP-/- mice versus WT mice, while splenic myeloid populations were similar in number in WT and BCAP-/- mice. Also, mixed chimeras generated with a 1:1 ratio of WT and BCAP-/- bone marrow exhibited a skewing towards BCAP-/- monocytes and neutrophils in the bone marrow, blood and spleen, showing a competitive advantage of BCAP-/- myeloid cells. Thus we hypothesized that BCAP regulates myeloid cell development. WT and BCAP-/- bone marrow had similar numbers of myeloid progenitors, including LSK (Lin-Sca1+cKit+) and CMP (Common Myeloid Progenitor) cells. However, in mixed bone marrow chimeras the progenitor populations were skewed toward BCAP-/- cells, showing that BCAP-/- progenitors out-compete their WT counterparts. In an in vitro myeloid colony forming unit assay, sorted BCAP-/- progenitors produced more cells than WT progenitors, supporting a cell-intrinsic role of BCAP in regulating myeloid differentiation. Also, during infection with Listeria monocytogenes, we observed increased splenic bacterial clearance and numbers of monocytes and neutrophils by day 2 post-infection in BCAP-/- mice compared to WT mice. Together, these data show that BCAP is a negative regulator of myeloid cell development.