title: The opposing roles of the transcription factor E2A and its antagonist Id3 that orchestrate and enforce the naive fate of T cells.
abstract: It is established that the transcription factor E2A and its antagonist Id3 modulate the checkpoints consisting of the precursor to the T cell antigen receptor (pre-TCR) and the TCR. Here we demonstrate that Id3 expression was higher beyond the pre-TCR checkpoint, remained high in naive T cells and showed a bimodal pattern in the effector-memory population. We show how E2A promoted T lineage specification and how pre-TCR-mediated signaling affected E2A genome-wide occupancy. Thymi in Id3-deficient mice had aberrant development of effector-memory cells, higher expression of the chemokine receptor CXCR5 and the transcriptional repressor Bcl-6 and, unexpectedly, T cell-B cell conjugates and B cell follicles. Collectively, our data show how E2A acted globally to orchestrate development into the T lineage and that Id3 antagonized E2A activity beyond the pre-TCR checkpoint to enforce the naive fate of T cells.
authors.affiliation: Department of Molecular Biology, University of California, San Diego, La Jolla, California, USA.
authors.forename: Masaki
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Richard R
authors.initials: RR
authors.lastname: Rivera
authors.forename: Kazuko
authors.initials: K
authors.lastname: Miyazaki
authors.forename: Yin C
authors.initials: YC
authors.lastname: Lin
authors.forename: Yasutoshi
authors.initials: Y
authors.lastname: Agata
authors.forename: Cornelis
authors.initials: C
authors.lastname: Murre
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000502:physiology*; D007156:Immunologic Memory; D016130:Immunophenotyping; D051796:Inhibitor of Differentiation Proteins / Q000502:physiology*; D017493:Leukocyte Common Antigens / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D054380:Receptors, CXCR5 / Q000032:analysis; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D051796:Inhibitor of Differentiation Proteins; D017493:Leukocyte Common Antigens; D011948:Receptors, Antigen, T-Cell; D054380:Receptors, CXCR5; C513179:CXCR5 protein, mouse; C075668:Tcf3 protein, mouse; C067679:Idb3 protein, mouse