The Id proteins are inhibitors of the basic-heiix-ioophelix (bHLH) transcription factors. in the B ceil lineage, the Id7 and ld2 genes are expressed in pro-6 ceils and down-regulated during differentiation. To determine the role of bHLH proteins and the significance of downregulation of Id genes in B ceil development, transgenie mice constitutiveiy expressing the Id7 gene were generated. Their phenotype suggests that B ceil deveiopment is impaired at an early stage. Primarily, these mice have few B220+ igM+ mature B or B220+ CD43-pre-B ceils in the bone marrow, reduced frequenciesof V (D) J and VJJ, recombination of the immunogiobuiin loci, and lower expression levels of the immunoglobuiin, RAG. 7, RAG-2, and 15 genes. introduction

The differentiation of 6 lymphoid cells is underlined by two major events: the rearrangement and the expression of immunoglobulin genes. These events are regulated in a temporal manner, such that the heavy chain locus is usually rearranged and then transcribed prior to the rearrangement and transcription of the light chain genes (Blackwell and Alt, 1988; Rolinkand Melchers, 1991). Regulators of these events include proteins that constitute the recombination machinery, such as RAG-l and RAG-2 (Schatz et al., 1989; Oettinger et al., 1990), and transcription factors of numerous families, such as the octamerbinding protein family (Staudt et al., 1988; Clerc et al., 1988) the basic-helix-loop-helix family (Murre et al., 1989) the re//NF-lcB family (Ghosh et al., 1990; Kieran et al., 1990; Nolan et al., 1991) and the ets family (Lopez et al., 1994). Each of these transcription factor families, which bind to the promoters and enhancers of the immunoglobulin genes, might be involved in activating expression of the immunoglobulin heavy chain, the light chain gene, or both, but it is not precisely clear at which stage of B cell development each factor exerts its action and whether different factors function separately or together at various stages.