THE HELIX-LOOP-HELIX GENE E2A IS REQUIRED FOR B-CELL FORMATION

Heterodimers between tissue-specific basic-helix-loop-helix proteins a nd the gene products of E2A play major roles in determining tissue-spe cific cell fate. To understand the broad role of E2A in development, w e have generated E2A mutant mice following homologous recombination in embryonic stem cells. Homozygous mutant mice develop to full term wit hout apparent abnormalities, but then display a high rate of postnatal death. The surviving mice show retarded postnatal growth. Detailed ex amination of hematopoiesis reveals that the homozygous mutant mice con tain no B cells while other lineages including T cell, granulocyte, ma crophage, and erythroid are intact. The block to B cell differentiatio n occurs prior to immunoglobulin gene D-H-J(H) rearrangement and the e xpression of the B lineage-specific marker B220. Surprisingly, heteroz ygous embryos contain, on average, about half as many B cells as wild- type embryos, suggesting the existence of a counting mechanism that tr anslates levels of E2A into numbers of B cells.