STAT3 positively regulates an early step in B-cell development

Abstract

Transcription factors are critical for instructing the development of B lymphocytes from multipotential progenitor cells in the bone marrow (BM). Here, we show that the absence of STAT3 impaired B-cell development. Mice selectively lacking STAT3 in BM progenitor cells displayed reduced numbers of mature B cells, both in the BM and in the periphery. The reduction in the B-cell compartment included reduced percentages and numbers of pro-B, pre-B, and immature B cells in the absence of STAT3, whereas the number of pre–pro-B cells was increased. We found that pro-B and pre-B–cell populations lacking STAT3 were hyporesponsive to IL-7 because of a decreased number of IL-7–responsive cells rather than decreased expression or signaling of IL-7Rα. Moreover, STAT3-deficient mice displayed enhanced apoptosis in the pro-B population when deprived of survival factors, suggesting that at least 2 mechanisms (impaired differentiation and enhanced apoptosis) are involved in the mutant phenotype. Last, BM transplantation confirmed that impaired B lymphopoiesis in the absence of STAT3 was caused by a cell autonomous defect. In sum, these studies defined a specific role for STAT3 in early B-cell development, probably acting at the pre–pro-B transition by contributing to the survival of IL-7–responsive progenitors.