Critical Role for the Oct-2/OCA-B Partnership in Ig-Secreting Cells

Abstract

B and T lymphocytes arise from a common precursor in the bone marrow, but ultimately acquire very different functions. The difference in function is largely attributable to the expression of tissue-specific transcription factors that activate discrete sets of genes. In previous studies we and others have shown that the specialized genes expressed by Ig-secreting cells cease transcription when these cells are fused to a T lymphoma. The extinguished genes include those encoding Ig, J chain, and the transcription factors Oct-2, PU.1, and the coactivator OCA-B. Remarkably, if we sustain Oct-2 expression during cell fusion, all the other tissue-specific genes of the Ig-secreting cell simultaneously escape silencing. This suggests that Oct-2 plays a central role in maintaining the gene expression program of these cells. In the present studies we have investigated the roles of the transcription factor PU.1 and the coactivator OCA-B within the hierarchy of regulatory factors that sustain Ig-secreting cell function. Our results show that OCA-B and Oct-2 are regulatory partners in this process and that PU.1 plays a subordinate role at this cell stage.

Epigenetic processes play a major role in B-cell-specific gene silencing in classical Hodgkin lymphoma

“…PU.1 is expressed earlier in the hematopoetic lineage compared with Oct1 and BOB.1/OBF.1; nevertheless, Oct2 and BOB.1/OBF.1 might be higher in the hierarchy of B-lineage-specific transcription factors than PU.1, because overexpression of Oct2 and/or BOB.1/OBF.1, but not PU.1, prevented extinguishing of B-cell-specific genes in plasmacytoma cells, fused to T lymphoma (immunoglobulin heavy chain [IgH], Oct2, and PU.1). 66 Our data on PU.1 and SYK reactivation in Oct2-overexpressing L428 cells treated with 5-aza-dC and the ability of PU.1 to reactivate SYK indicate their important role in the reactivation process. Both SYK and PU.1 were reactivated in KM-H2 and L1236 cells, and both were absent or very low in L428 cHL cells.…”

BOB.1/OBF.1 - A Critical Regulator of B Cell Function

“…However, Rag 1 -/-reconstitution experiments with BOB.1/OBF.1 B cells in combination with wildtype T cells revealed an B cell autonomous defect [38]. Despite the convincing evidence on the role of Oct proteins and BOB.1/OBF.1 in Ig gene transcription [80,81], the Ig expression at the early stages of B cell development is largely unaffected in BOB.1/OBF.1-deficient mice [82]. Surprisingly, in mice simultaneously deficient for BOB.1/OBF.1 and Oct2, B cell development to the IgM positive stage as well as primary immunoglobulin gene transcription also were not affected [82].…”

Octamer-binding transcription factors: genomics and functions

“…Interaction with tissue-specific cofactors enables the ubiquitously expressed Oct1 to contribute to tissue-specific gene expression. The partnership between Oct2 and Bob-1 has been shown to play a critical role in sustaining Ig-secretin cell functions (127). …”