Involvement of the E2A basic helix-loop-helix protein in immunoglobulin heavy chain class switching

The role of E2A-PBX1 in leukemogenesis

“…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). E2A is also an important regulator of T cell development, and E2A-de®cient mice showed defects in multiple stages of thymocyte selection and di erentiation (Bain et al, 1997;Barndt et al, 2000;Rivera et al, 2000).…”

Impaired Immune Responses and B-Cell Proliferation in Mice Lacking the Id3 Gene

“…E2A proteins were detected in all stages of B-cell development (67). Immunostaining also revealed an upregulation of E2A in the dark zone of the germinal center, where hypermutation and isotype switching occur (27,49). Ectopic expression of Id1 in a mature B-cell line inhibited the ability of cells to undergo spontaneous isotype switching, suggesting a functional interaction between Id and E2A proteins (27).…”

“…Immunostaining also revealed an upregulation of E2A in the dark zone of the germinal center, where hypermutation and isotype switching occur (27,49). Ectopic expression of Id1 in a mature B-cell line inhibited the ability of cells to undergo spontaneous isotype switching, suggesting a functional interaction between Id and E2A proteins (27). However, a role for Id1 or Id2 in mature B cells is questioned by their reduced levels of expression in mature B cells (60,66).…”

Characterization of ABF-1, a Novel Basic Helix-Loop-Helix Transcription Factor Expressed in Activated B Lymphocytes

“…Furthermore, B-cell development is inhibited in transgenic mice that overexpress the E2A inhibitor, Id1 (66). E2A-like molecules have also been suggested to play a role in Ig switching, since overexpression of Id1 in B-cell lines interfered with the ability of these cells to undergo isotype switching (22). During thymocyte development, both E2A and HEB gene products which bind as heterodimers to the E2 box site are expressed (1a, 59).…”