title: Id3 Orchestrates Germinal Center B Cell Development.
abstract: Previous studies have demonstrated that E proteins induce activation-induced deaminase (AID) expression in activated B cells. Here, we examined the role of Id3 in germinal center (GC) cells. We found that Id3 expression is high in follicular B lineage cells but declines in GC cells. Immunized mice with Id3 expression depleted displayed a block in germinal center B cell maturation, showed reduced numbers of marginal zone B cells and class-switched cells, and were associated with decreased antibody titers and lower numbers of plasma cells. In vitro, Id3-depleted B cells displayed a defect in class switch recombination. Whereas AID levels were not altered in Id3-depleted activated B cells, the expression of a subset of genes encoding signaling components of antigen receptor-, cytokine receptor-, and chemokine receptor-mediated signaling was significantly impaired. We propose that during the GC reaction, Id3 levels decline to activate the expression of genes encoding signaling components that mediate B cell receptor- and or cytokine receptor-mediated signaling to promote the differentiation of GC B cells.
authors.affiliation: Department of Molecular Biology, University of California, San Diego, La Jolla, California, USA.
authors.forename: Shuwen
authors.initials: S
authors.lastname: Chen
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.affiliation: Department of Molecular Biology, University of California, San Diego, La Jolla, California, USA.
authors.forename: Vivek
authors.initials: V
authors.lastname: Chandra
authors.affiliation: Department of Molecular Biology and Bioinformatics and Department of Medicine, University of California, San Diego, La Jolla, California, USA.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Fisch
authors.affiliation: Department of Molecular Biology and Bioinformatics and Department of Medicine, University of California, San Diego, La Jolla, California, USA.
authors.forename: Aaron N
authors.initials: AN
authors.lastname: Chang
authors.affiliation: Department of Molecular Biology, University of California, San Diego, La Jolla, California, USA murre@biomail.ucsd.edu.
authors.forename: Cornelis
authors.initials: C
authors.lastname: Murre
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D003564:Cytidine Deaminase / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D018858:Germinal Center / Q000378:metabolism*; D007114:Immunization / Q000379:methods*; D017578:Immunoglobulin Class Switching; D051796:Inhibitor of Differentiation Proteins / Q000235:genetics / Q000378:metabolism*; D008213:Lymphocyte Activation; D051379:Mice; D015398:Signal Transduction; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D051796:Inhibitor of Differentiation Proteins; C067679:Idb3 protein, mouse; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase