Note that exon 1, as shown in this panel, is not included in the RefSeq (Mouse mm9, July 2007) map of mRNA, but is represented in alternate transcripts ENSMUST00000120135 and ENSMUST00000118756 in the Ensembl database. Oct2 modulates B cell receptor signaling by fine-tuning Syk expression A microarray screen for Oct2-dependent genes identified the tyrosine kinase as a potential target gene. and others have shown that Oct2 and Obf1 are required for B cells to mature fully gene expression, thus influencing B cell receptor signaling, and that Oct2 loss blocks expression as a result of incomplete B cell maturation. Upon IL4 signaling, Stat6 up-regulates Obf1, indirectly via Xbp1, to enable plasma cell differentiation. Thus, Oct2 and Obf1 enable B cells to respond normally to antigen receptor signals, to express surface receptors that mediate physical conversation with T cells, or to produce and respond to cytokines that are critical drivers of B cell and T cell differentiation during a humoral immune response. gene. It was one of the first cell type-specific transcription factors identified and cloned (1). As indicated by its name, it is a founding member of a family of DNA binding proteins concurrently discovered, that share a conserved bipartite DNA binding domain name comprising a homeobox-like domain name and a second conserved sequence entitled the POU domain name, for the gene, which is also known as OCA-B and Bob.1 was subsequently cloned using a yeast 1-hybrid screen for B cell proteins that physically interact with Oct1 or Oct2 Rabbit Polyclonal to NOTCH2 (Cleaved-Val1697) (5C7). While Oct1/Oct2 and Obf1 share the capacity to bind to and activate genes adjacent to octamer motifs, they are selective in the genes to which they bind. The selectivity of target gene binding is determined, in part, Atglistatin by the sequence of the octamer motif, and whether it conforms to one of two classes of site, designated PORE and MORE motifs (8). Whether binding mediates activation or repression is also influenced by the participation of cofactors [reviewed by Tantin (9)], including Obf1, which can potentiate the transactivation potential of Oct1 and Oct2 (8, 10). Oct2 is usually expressed primarily but not exclusively in the B cell lineage, where it increases with cellular activation Atglistatin (11). Neurons, macrophages, and T cells have also been shown to express (12C18). Oct2 is required for post-natal survival (19), so must regulate critically important genes outside of the immune system. These will not be discussed here. The gene is large, displays complex splicing patterns, and encodes protein isoforms with multiple essential activation domains (20C22). Oct2 is largely localized to the nucleus. expression is mostly restricted to B lineage cells, where it is also highly induced upon activation (23). Zwilling et al. (24) have reported expression in T cells, but myeloid cells do not express (15). A small protein of ~35?kDa, Obf1 is found in both the nucleus and cytoplasm, where a proportion may be tethered to the cell membrane after post-translational myristoylation (25), and a potential role for membrane-associated Obf1 in B cell receptor (BCR) signaling has been proposed (26). A series of studies have shown that Oct2 and Obf1 are required for full functional and phenotypic maturation of B cells. In single knockout (KO) mice of each gene, peripheral B cells are numerically reduced and display some features of immature transitional cells (27, 28). The peritoneal B1 and splenic marginal zone (MZ) populations are missing in mice (27, 29). mice are viable and fertile, but show B cell developmental defects (30, 31), have an expanded B1 cell population Atglistatin (32). They also lack MZ B cells (33) and completely fail to produce germinal centers (GCs), the sites of cognate Atglistatin B Atglistatin cell:T cell interaction and expansion, upon immunization, or infection (34C37). Both Oct2- and Obf1-deficient splenic B cells display aberrant responses to BCR signaling and other characteristics of immature B cells (27, 34, 38). Oct2-deficient B cells also fail to respond to lipopolysaccharide (LPS), which signals through TLR4 (38). and have identified a number of genes regulated by the two factors. Oct2 directly regulates the gene encoding CD36, a class B scavenger receptor family (40), but only in B cells, not in macrophages or dendritic cells (41C43). However, no role for CD36 in B cells has been determined (44). Oct2-deficent B cells have been shown to be defective in their responses to the.