title: E2A activity is induced during B-cell activation to promote immunoglobulin class switch recombination.
abstract: The basic helix-loop-helix protein, E2A, is required for proper early B lymphopoiesis. Specifically, in E2A-deficient mice, B-cell development is blocked at the progenitor stage prior to the onset of immunoglobulin (Ig) V(D)J recombination. Here, we demonstrate that E2A plays an additional role during peripheral B lymphopoiesis. Upon activation of primary mature B lymphocytes, both E2A protein levels and DNA-binding activity are induced. Furthermore, we show that mature B cells, expressing a dominant-negative E2A antagonist, proliferate normally in response to mitogenic signaling and appropriately express the early and late activation markers CD69, CD44, IgD and B220. However, in the absence of E2A activity, B lymphocytes are blocked in their ability to express secondary Ig isotypes. We demonstrate that the defect lies at the level of DNA rearrangements between the Ig switch regions. These data suggest that E2A is an essential target during B-cell activation and its induction is required to promote Ig class switch recombination.
authors.affiliation: Department of Biology, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: M W
authors.initials: MW
authors.lastname: Quong
authors.forename: D P
authors.initials: DP
authors.lastname: Harris
authors.forename: S L
authors.initials: SL
authors.lastname: Swain
authors.forename: C
authors.initials: C
authors.lastname: Murre
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology*; D015415:Biomarkers / Q000032:analysis; D002467:Cell Nucleus / Q000502:physiology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005434:Flow Cytometry; D018257:Helix-Loop-Helix Motifs; D018960:Hyaluronan Receptors / Q000032:analysis; D007072:Immunoglobulin D / Q000032:analysis; D007132:Immunoglobulin Isotypes / Q000235:genetics*; D007134:Immunoglobulin Switch Region; D051796:Inhibitor of Differentiation Proteins; D037181:Lectins, C-Type; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins; D016133:Polymerase Chain Reaction; D011995:Recombination, Genetic / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000276:immunology; D051820:TCF Transcription Factors; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D015415:Biomarkers; D004268:DNA-Binding Proteins; D018960:Hyaluronan Receptors; D007072:Immunoglobulin D; D007132:Immunoglobulin Isotypes; D051796:Inhibitor of Differentiation Proteins; D037181:Lectins, C-Type; D009363:Neoplasm Proteins; D051820:TCF Transcription Factors; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors; D000099192:CD69 Antigens; C544912:TCF7L1 protein, human; C544913:Tcf7l1 protein, mouse; C075640:ID3 protein, human