The transcription factor early growth response 1 (Egr-1) advances differentiation of pre-B and immature B cells

In mature B lymphocytes, the zinc finger transcription factor early growth response 1 (Egr-1) is one of the many immediate-early genes induced upon B cell antigen receptor engagement. However, its role during earlier stages o f lymphopoiesis has remained unclear, By examining bone marrow B cell subse ts, we found Egr-1 transcript in pro/pre-B and immature B lymphocytes,. and Egr-1 protein in pro/pre-B-I cells cultivated on stroma cells ill the pres ence of interleukin (IL)-7. In recombinase-activating gene (RAG)-2-deficien t mice overexpressing an Egr-1 transgene in the B lymphocyte lineage, pro/p re-B-I cells could differentiate past a developmental block at the B220(low ) BP-1(-) stage to the stage of B220(low) BP-1(+) pre-B-I cells, but not fu rther to the B220(low) BP-1(+) CD25(+) stage of pre-B-II cells. Therefore, during early B lymphopoiesis progression front the B220(low) BP-1(-) IL-2R( -) pro/prw-B-I stage to the B220(low) BP-1(+) IL-2R(+) pre-B-II stage seems to occur in at least two distinct steps, and the first step to the stage o f B220(low) BP-1(+) pre-B-I cells can be promoted by the overexpression of Egr-1 alone. Wild-type mice expressing an Egr-1 transgene had increased pro portions of mature immunoglobulin (Ig)M+ B220(high) and decreased proportio ns of immature IgM(+) B220(low) bone marrow B cells. Since transgenic and c ontrol precursor B cells show comparable proliferation patterns, overexpres sion of Egr-1 seems also to promote entry into the mature B cell stage. Ana lysis of changes in the expression pattern of potential Egr-1 target genes revealed that Egr-1 enhances the expression of the aminopeptidase BP-1/6C3 in pre-B and immature B cells and upregulates expression of the orphan nucl ear receptor nur77 in IgM(+) B cells.