B-LYMPHOCYTE DEVELOPMENT IS REGULATED BY THE COMBINED DOSAGE OF 3 BASIC HELIX-LOOP-HELIX GENES, E2A, E2-2, AND HEB

B-lymphocyte development requires the basic helix-loop-helix proteins encoded by the E2A gene. In this study, the control mechanism of E2A w as further explored by disruption of the E2A-related genes, E2-2 and H EB, In contrast to E2A, E2-2 and HEB are not essential for the establi shment of the B-cell lineage. However, both E2-2 and HEB are required for the generation of the normal numbers of pro-B cells in mouse embry os. Breeding tests among mice carrying different mutations revealed th at E2-2 and HEB interact with E2A in many developmental processes incl uding the generation of B cells, Specifically, mice transheterozygous for any two mutations of these three genes produced fewer pro-B cells than the singly heterozygous littermates. This study indicates that B- cell development is dependent not only on an essential function provid ed by the EW gene but also on a combined dosage set by E2A, E2-2, and HEB.