The immediate-early gene egr-1 (also known as NGFI-A, krox24, zif268, and tis8) encodes a transcription factor containing three tandem zinc finger motifs that bind to GC-rich DNA elements in the promoters of a range of target genes to activate their transcription (1). egr-1 expression is elicited in response to a diverse variety of signals, including growth factors, cytokines, lipopolysaccharide, serum, irradiation, stress, hypoxia, and urea, in many cell types, including neuronal cells, epithelial cells, fibroblasts, myeloid cells, and T and B lymphocytes (2-9). In many studies, Egr-1 was found to be associated with cell proliferation, differentiation, and transformation (3, 10 -14). Egr-1 was also shown to induce apoptosis in certain cell types in response to irradiation by activating p53 (15) or PTEN expression (16). Yu et al. (17) reported that differential post-translational modification of Egr-1 (acetylation versus phosphorylation) is likely responsible for its different roles in promoting growth versus apoptosis in response to serum and UV irradiation. Moreover, Egr-1 is shown to be important for production of pro-inflammatory cytokines such as interleukin-1, interleukin-13, and tumor necrosis factor as well as chemokines (18 -20).In normal mature B lymphocytes, signaling through the B cell receptor (BCR) 2 induces rapid and transient expression of egr-1 (6), but its importance for subsequent B cell activation and proliferation is unknown. In contrast, BCR engagement in immature B lymphoma cells fails to induce egr-1 expression, and the lymphoma cells undergo growth inhibition and apoptosis (21). Thus, BCR-induced positive versus negative signals are reflected in the differential expression of egr-1. Interestingly, an immature B lymphoma cell line (BKS-2) constitutively expresses high levels of Egr-1, and antisense oligodeoxynucleotides (ODNs) to Egr-1 inhibit BKS-2 cell growth (14). BCR signaling, which causes growth arrest and apoptosis of BKS-2 cells, also down-regulates egr-1 (14). The down-regulation of Egr-1 and growth inhibition caused by anti-IgM antibody are reversed by CpG ODN (22). These data suggest a positive correlation between the levels of Egr-1 and growth of B lymphoma cells. An examination of the microarray data published by Alizadeh et al. (23) revealed that egr-1 expression is elevated in ϳ35% of human diffuse large B lymphoma cells, supporting the notion that Egr-1 is important for B lymphoma cell growth.Several studies in different cell lines have shown that the rapid induction of Egr-1 with various stimuli is mediated * This work was supported by National Institutes of Health Grant 5P01CA092372 (to S. B.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C.