C-Myb is crucial for B-lymphocyte development (138.30)

Abstract

Abstract c-Myb is abundantly expressed in lymphocyte progenitors yet little is known about c-Myb function during lymphocyte development due to the embryonic lethality of Myb null mutations. We have targeted the murine Myb locus with loxP sites for conditional deletion and crossed Mybff mice to the Mb1Cre and CD19Cre strains to ablate c-Myb expression during different stages of B cell development. Mb1Cre mediated deletion begins in pre-pro-B cells and is complete by the pro-B cell stage. We detect a no decrease in the number pre-pro-B cells but <1% the normal number of CD19+ B-lineage cells at any subsequent stage of development, demonstrating that c-Myb is essential for the development past the point of commitment to the B cell lineage. In Mybf/f CD19Cre mice, B-lineage cells are reduced in number by 80% and blocked in transition from pro-B to pre-B cells, resulting in about 10% the normal number of IgM+ bone marrow B cells. c-Myb deficient B cells are hyporesponsive to IL-7 in methylcellulose cloning assays and in vitro proliferation assays, suggesting that at least part of the defect in pro-B to pre-B cell transition is due to a defect in the IL-7 signaling pathway.