Helix-loop-helix transcription factor E47 activates germ-line immunoglobulin heavy-chain gene transcription and rearrangement in a pre-T-cell line.

Abstract

E47 is a helix-loop-helix transcription factor that binds to sites in the immunoglobulin heavy-chain and K light-chain gene enhancers. Other proteins of this type are involved in cell-type determination. A possible role for E47 in B-cell development was tested by overexpressing a cDNA encoding E47 in the pre-T-cell line 2017. We found a dramatic activation of a germ-line heavy-chain gene transcript in these stable transfectants and an equally large induction of immunoglobulin D-to-J rearrangement, the first recognized step in B-cell development. Germ-line K light-chain gene transcription and rearrangement were unaffected, but transcription of the recombination-activating genes RAG-1 and RAG-2 and the lymphoid-specific transcription factor Oct-2 was increased. These T cells did not transcribe their rearranged DJ alleles, however, and failed to progress to the next stage of heavy-chain gene assembly, V-to-DJ rearrangement. Because transcription factor E47 can induce pre-T cells to carry out events of B-cell differentiation, it may be a crucial determinant of the earliest stages of B-cell development.

Loss of B cell identity correlates with loss of B cell-specific transcription factors in Hodgkin/Reed-Sternberg cells of classical Hodgkin lymphoma

“…However, unlike the other HRS cell lines, very low signals of Cm transcripts were already present in the HD-LM2 cells prior to transfection. Our findings, therefore, confirm that forced expression of E47 in non-B cells can induce transcription from unrearranged IgH loci that are primed for transcription (Schlissel et al, 1991;Choi et al, 1996).…”

Antibody Repertoire Development in Fetal and Neonatal Piglets. II. Characterization of Heavy Chain Complementarity-Determining Region 3 Diversity in the Developing Fetus

“…Therefore, such a spectratype can be interpreted to mean that 1) such cells represent an epiphenomenon in which B cell precursors that migrate to the thymus do not encounter selection pressures for those with in-frame rearrangements; 2) the observed spectratype is derived from thymocytes that have rearranged their heavy chain Ig segments and carry them in a nonfunctional state; or 3) the thymus is a true site of B cell lymphogenesis, and our studies have captured pro-B cells before selection and/or migration to other sites where selection occurs. Ig, specifically Ig DJ rearrangements, have been reported in human thymocytes (59,60). To rule out the second possibility in swine, we bulk-sorted thymocytes from a late term fetus and T cells from spleen.…”

The role of E2A-PBX1 in leukemogenesis

“…Expression of E12 in a macrophage cell line also directs the activation of a variety of B lineage genes, including the transcription factor EBF-1, the surrogate light chain l5 and Rag-1 (Kee and Murre, 1998). In addition to activating the expression of B cell-speci®c genes, E2A also plays a direct role in Ig gene rearrangement, which constitutes a critical step in B cell development (Bain et al, 1999;Romanow et al, 2000;Schlissel et al, 1991). At later stages of B cell maturation, E2A functions to regulate Ig class switch recombination in peripheral mature B cells (Goldfarb et al, 1996;Quong et al, 1999).…”