title: The Transcription Factor AP4 Mediates Resolution of Chronic Viral Infection through Amplification of Germinal Center B Cell Responses.
abstract: B cells diversify and affinity mature their antigen receptor repertoire in germinal centers (GCs). GC B cells receive help signals during transient interaction with T cells, yet it remains unknown how these transient T-B interactions in the light zone sustain the subsequent proliferative program of selected B cells that occurs in the anatomically distant dark zone. Here, we show that the transcription factor AP4 was required for sustained GC B cell proliferation and subsequent establishment of a diverse and protective antibody repertoire. AP4 was induced by c-MYC during the T-B interactions, was maintained by T-cell-derived interleukin-21 (IL-21), and promoted repeated rounds of divisions of selected GC B cells. B-cell-specific deletion of AP4 resulted in reduced GC sizes and reduced somatic hypermutation coupled with a failure to control chronic viral infection. These results indicate that AP4 integrates T-cell-mediated selection and sustained expansion of GC B cells for humoral immunity.
authors: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors: Chun
authors: C
authors: Chou
authors: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors: Daniel J
authors: DJ
authors: Verbaro
authors: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors: Elena
authors: E
authors: Tonc
authors: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors: Melanie
authors: M
authors: Holmgren
authors: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors: Marina
authors: M
authors: Cella
authors: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors: Marco
authors: M
authors: Colonna
authors: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors: Deepta
authors: D
authors: Bhattacharya
authors: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA. Electronic address: tegawa@wustl.edu.
authors: Takeshi
authors: T
authors: Egawa
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation / Q000502:physiology; D005260:Female; D018858:Germinal Center / Q000276:immunology*; D007378:Interleukins / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology; D014157:Transcription Factors / Q000276:immunology*; D014777:Virus Diseases / Q000276:immunology*; D000098546:Interleukin-21
chemical_list: D007378:Interleukins; D014157:Transcription Factors; C562117:transcription factor AP4, mouse; D000098546:Interleukin-21