Oct-2 is required early in T cell-independent B cell activation for G1 progression and for proliferation

Corcoran, Lynn M.; Karvelas, Maria

doi:10.1016/1074-7613(94)90035-3

Cited by 101 publications

(99 citation statements)

References 55 publications

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“…The evaluation of the specific role of Oct-2 in B cells has been complicated by the fact that Oct-2 knockout mice die shortly after birth, and there is partial compensation by Oct-1. However, when scid mice were reconstituted with Oct-2 Ϫ/Ϫ B cells, there was a profound defect in circulating levels of Igs of all isotypes, except for IgA (69).…”

Section: Discussionmentioning

confidence: 99%

NF-κB and Oct-2 Synergize to Activate the Human 3′ Igh hs4 Enhancer in B Cells

Sepúlveda

Emelyanov

Birshtein

2004

The Journal of Immunology

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In B cells, the Igh gene locus contains several DNase I-hypersensitive (hs) sites with enhancer activity. These include the 3′ Igh enhancers, which are located downstream of the Cα gene(s) in both mouse and human. In vivo experiments have implicated murine 3′ enhancers, hs3B and/or hs4, in class switching and somatic hypermutation. We previously reported that murine hs4 was regulated by NF-κB, octamer binding proteins, and Pax5 (B cell-specific activator protein). In this study we report that human hs4 is regulated differently. EMSAs and Western analysis of normal B cells before and after stimulation with anti-IgM plus anti-CD40 showed the same complex binding pattern formed by NF-κB, Oct-1, and Oct-2 (but not by Pax5). A similar EMSA pattern was detected in mature human B cell lines (BL-2, Ramos, and HS-Sultan) and in diffuse large B cell lymphoma cell lines, although yin yang 1 protein (YY1) binding was also observed. We have confirmed the in vivo association of these transcription factors with hs4 in B cells by chromatin immunoprecipitation assays. The diffuse large B cell lymphoma cell lines had a distinctive slow-migrating complex containing YY1 associated with Rel-B. We have confirmed by endogenous coimmunoprecipitation an association of YY1 with Rel-B, but not with other NF-κΒ family members. Transient transfection assays showed robust hs4 enhancer activity in the mature B cell lines, which was dependent on synergistic interactions between NF-κB and octamer binding proteins. In addition, human hs4 enhancer activity required Oct-2 and correlated with expression of Oct coactivator from B cells (OCA-B).

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Section: Discussionmentioning

confidence: 99%

NF-κB and Oct-2 Synergize to Activate the Human 3′ Igh hs4 Enhancer in B Cells

Sepúlveda

Emelyanov

Birshtein

2004

The Journal of Immunology

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“…12,13 On the other hand, OCT.2 expression is restricted to B cells and neuronal cells, 14 and plays an important role in Ig promoter transactivation, as has been demonstrated by transfection experiments. 15 They both participate in the control of important B-specific genes involved in proliferation and differentiation, [16][17][18][19][20] such as Ig genes, CD20, CD79a and J chain. Transfection studies have demonstrated that OCT.1 can compensate the absence of OCT.2.…”

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confidence: 99%

Analysis of transcription factor OCT.1, OCT.2 and BOB.1 expression using tissue arrays in classical Hodgkin's lymphoma

et al. 2004

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Hodgkin's lymphoma can be considered in most cases a B-cell lymphoma due to the presence of potentially functional immunoglobulin (Ig) gene rearrangements in the neoplastic cells. In contrast to lymphocytepredominant Hodgkin's lymphoma, Hodgkin/Reed-Sternberg (HRS) cells from classical Hodgkin's lymphoma have low frequency of B-cell marker expression and lack Ig light and Ig heavy messenger RNA. Recent studies have shown transcription machinery deficiency in Hodgkin's lymphoma caused by an absence of the transcription factors OCT.1, OCT.2 and/or BOB.1. By using the tissue microarray technique, we have performed an immunohistochemical study of OCT.1, OCT.2 and BOB.1 in 325 classical Hodgkin's lymphoma cases. The results have been correlated with the expression of the B-cell markers CD20, CD79a, B-cell-specific activator protein (BSAP) and MUM.1, the presence of Epstein-Barr virus and the histological subtype. The percentage of CD20 and CD79a positivity was low (18 and 18%, respectively), whereas MUM.1 and BSAP were positive in the majority of cases. Considering the positive cases with independence of the intensity of staining, 62% of them expressed OCT.2, 59% OCT.1 and 37% BOB.1. Nevertheless, when we considered only the strongly positive cases, the results were similar to those previously described by others. No statistical association was found between the transcription factor expression, histological subtype and Epstein-Barr virus presence. To our knowledge, this is the largest series of classical Hodgkin's lymphoma cases in which the expression of transcription factors has been studied. We have found a notorious percentage of cases displaying weak positivity for OCT.2 and BOB.1 factors in HRS cells. We propose that other mechanisms different from the absence of transcription factors OCT.2 and BOB.1 might be involved in the control of Ig transcription and B lineage in classical Hodgkin's lymphoma.

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“…Mice lacking either or both of these genes produced surface Ig-positive B cells, demonstrating that neither Oct-2 nor OCA-B is essential for the activation of Ig genes nor for early events in B cell development (25)(26)(27)(28). However, these knockout mice showed defects in events that commonly occur after B cell activation (i.e., postantigenic challenge), making evident unique functions for Oct-2 and OCA-B in late-stage cells (27)(28)(29)(30)(31)(32).system. Our laboratory showed that if we sustained expression of just this one protein (Oct-2), the Pou2f2 locus and all other assayed, B cell-specific genes simultaneously escaped silencing (33).…”

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confidence: 99%

Unique Function for Carboxyl-Terminal Domain of Oct-2 in Ig-Secreting Cells

Sharif

Radomska

Miller

et al. 2001

The Journal of Immunology

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The activity of Ig gene promoters and enhancers is regulated by two related transcription factors, Oct-1 (ubiquitous) and Oct-2 (B lineage specific), which bind the octamer motif (ATTTGCAT) present in these elements. As Ig promoter-binding factors, Oct-1 and Oct-2 each work together with a B lymphocyte-specific cofactor OCA-B/OBF-1/Bob-1 that interacts with them through their POU (DNA-binding) domains. Because both can mediate Ig promoter activity in B cells, there has been some question as to whether these two octamer-binding factors serve distinct functions in lymphocytes. We have shown previously that the silencing of B lymphocyte-specific genes in plasmacytoma × T lymphoma hybrids can be prevented by preserving Oct-2 expression. The pronounced effect of this transcription factor on the phenotype of plasmacytoma × T lymphoma hybrids established a critical role for Oct-2 not only in maintaining Ig gene expression, but in maintaining the overall genetic program of Ig-secreting cells. In the present study, we have explored the functional differences between Oct-1 and Oct-2 using chimeric Oct-1/Oct-2 proteins in cell fusion assays. Our results provide further evidence for an essential role for Oct-2 in Ig-secreting cells and identify the C-terminal domain of Oct-2 as responsible for its unique function in these cells.

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Oct-2 is required early in T cell-independent B cell activation for G1 progression and for proliferation

Cited by 101 publications

References 55 publications

NF-κB and Oct-2 Synergize to Activate the Human 3′ Igh hs4 Enhancer in B Cells

NF-κB and Oct-2 Synergize to Activate the Human 3′ Igh hs4 Enhancer in B Cells

Analysis of transcription factor OCT.1, OCT.2 and BOB.1 expression using tissue arrays in classical Hodgkin's lymphoma

Unique Function for Carboxyl-Terminal Domain of Oct-2 in Ig-Secreting Cells

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