摘要
B cell development in bone marrow is a precisely regulated complex process.Through successive stages of differentiation,which are regulated by a multitude of signaling pathways and an array of lineage-specific transcription factors,the common lymphoid progenitors ultimately give rise to mature B cells.Similar to early thymocyte development in the thymus,early B cell development in bone marrow is critically dependent on IL-7 signaling.During this IL-7-dependent stage of differentiation,several transcription factors,such as E2A,EBF1,and Pax5,among others,play indispensable roles in B lineage specification and maintenance.Although recent studies have implicated several other transcription factors in B cell development,the role of NFATc1 in early B cell developmental stages is not known.Here,using multiple gene-manipulated mouse models and applying various experimental methods,we show that NFATc1 activity is vital for early B cell differentiation.Lack of NFATc1 activity in pro-B cells suppresses EBF1 expression,impairs immunoglobulin gene rearrangement,and thereby preBCR formation,resulting in defective B cell development.Overall,deficiency in NFATc1 activity arrested the pro-B cell transition to the pre-B cell stage,leading to severe B cell lymphopenia.Our findings suggest that,along with other transcription factors,NFATc1 is a critical component of the signaling mechanism that facilitates early B cell differentiation.
