Cellular iron metabolism regulatory molecule FBXL5 contributes to B cell development in mice

Iron metabolism is essential for many biological processes such as oxygen transport, DNA replication and so on. FBXL5, the central molecule in cellular iron metabolism, is essential for hematopoietic stem cell maintenance. However, the role of FBXL5 in hematopoiesis remained to be elucidated. Here we found that the mice lacking FBXL5 in immune cells showed decrease in B cells and increase in myeloid cells. Analysis of conditional FBXL5 KO in B cell lineage also revealed B cell reduction and pro-B cell accumulation in bone marrow. To explore the mechanism of pro-B cell accumulation in FBXL5 KO, we conducted RNA sequencing using total RNA from pro-B cells. Some ROS related genes were differentially increased, suggesting that FBXL5 deletion which leads to excess ferrous iron in pro-B cells and causes ROS production and blockage for the pre-B cell differentiation. Our study suggests that FBXL5 plays an important role in early B cell development.