Oct-2, although not required for early B-cell development, is critical for later B-cell maturation and for postnatal survival.

Abstract

Oct-2, a POU homeo domain transcription factor, is believed to stimulate B-cell-restricted expression of immunoglobulin genes through binding sites in immunoglobulin gene promoters and enhancers. To determine whether Oct-2 is required for B-cell development or function, or has other developmental roles, the gene was disrupted by homologous recombination. Oct-2 -/-mice develop normally but die within hours of birth for undetermined reasons. Mutants contain normal numbers of B-cell precursors but are somewhat deficient in IgM + B cells. These B cells have a marked defect in their capacity to secrete immunoglobulin upon mitogenic stimulation in vitro. Thus, Oct-2 is not required for the generation of immunoglobulin-bearing B cells but is crucial for their maturation to immunoglobulin-secreting cells and for another undetermined organismal function.

Essential functions of Pax5 (BSAP) in pro-B cell development: difference between fetal and adult B lymphopoiesis and reduced V-to-DJ recombination at the IgH locus.

“…The availabil ity of homogeneous pre-BI cell populations differing only by the presence or absence of Pax5 made it possible to investigate whether BSAP regulates the expression of other known transcription factors. As shown by the RNase protection experiment in Figure 6, the expression of the transcription factors PU.l (Scott et al 1994), Ikaros (Georgopoulos et al 1994), EBF (Lin and Grosschedl 1995), E2A (Bain et al 1994;Zhuang et al 1994), Sox-4 (Schilham et al 1996), Oct-1 (Sturm et al 1988), Oct-2 (Corcoran et al 1993), and OBF-1 (Kim et al 1996;Schubart et al 1996) was unaffected at the mRNA level by the absence of Pax5. Similarly, the Pax5 mutation did nei ther influence transcription of the recombination acti vating genes RAG-1 (Schatz et al 1989) andRAG-2 (Oettinger et al 1990) nor expression of the germ-line tran script Ip which initiates within the IgH enhancer region (Lennon and Perry 1985).…”

“…However, a different situation prevails in fetal liver where PaxS is already required for full commitment to the B-lymphoid lineage. Progression of B-cell develop ment to the small pre-B-cell stage is furthermore depen dent on the function of the transcription factor Sox-4 (Schilham et al 1996), whereas Oct-2, OBF-1, and the pSO subunit of NF-KB have critical roles in the activation of mature B-cells to undergo plasma cell differentiation (Corcoran et al 1993;Sha et al 199S;Kim et al 1996;Schubart et al 1996). Importantly, the expression of none of these regulatory genes was affected in PaxS-de ficient pre-BI cells.…”

HDAC inhibitors augment cytotoxic activity of rituximab by upregulating CD20 expression on lymphoma cells

“…43,44 However, genetic studies using knockout mice indicate that Oct-2 is dispensable for early B-cell development and does not affect the baseline expression of CD20 in immature B lymphocytes. 45 In our pilot experiments, HDAC inhibitors reduced the expressions of PU.1 and USF1 to nearly undetectable levels (data not shown). We therefore focused on the region harboring the binding sites of Sp1 and NF-kB (À726 to À315) in this study.…”

Non-cell autonomous induction of apoptosis and loss of posterior structures by activation domain-specific interactions of Oct-1 in the Xenopus embryo

“…Pit-1 function appeared to be critical for expression of pituitary-specific effector genes and for proliferation or survival of three anterior pituitary cell types (reviewed by Anderson and Rosenfeld (1994)). Oct-2 proved to serve a critical function in B-cell maturation (Corcoran et al, 1993), and the unc-86 gene product is important for lineage-dependent neuronal specification (Finney and Ruvkun, 1990). The role of Oct-1 during development, however, has remained elusive.…”

“…Functions during embryonic development have been established for three of the initially identified POU domain proteins , i.e. for Pit-1, Oct-2 and Unc-86 (Finney and Ruvkun, 1990;Corcoran et al, 1993;Andersen and Rosenfeld, 1994), as well as for a number of more recently identified POU domain transcription factors Shimazaki et al, 1993;Takeda et al, 1994;Bhat et al, 1995;Nakai et al, 1995;Schonemann et al, 1995;Witta et al, 1995;Yeo et al, 1995). Pit-1 function appeared to be critical for expression of pituitary-specific effector genes and for proliferation or survival of three anterior pituitary cell types (reviewed by Anderson and Rosenfeld (1994)).…”