title: High levels of SOX5 decrease proliferative capacity of human B cells, but permit plasmablast differentiation.
abstract: Currently very little is known about the differential expression and function of the transcription factor SOX5 during B cell maturation. We identified two new splice variants of SOX5 in human B cells, encoding the known L-SOX5B isoform and a new shorter isoform L-SOX5F. The SOX5 transcripts are highly expressed during late stages of B-cell differentiation, including atypical memory B cells, activated CD21low B cells and germinal center B cells of tonsils. In tonsillar sections SOX5 expression was predominantly polarized to centrocytes within the light zone. After in vitro stimulation, SOX5 expression was down-regulated during proliferation while high expression levels were permissible for plasmablast differentiation. Overexpression of L-SOX5F in human primary B lymphocytes resulted in reduced proliferation, less survival of CD138neg B cells, but comparable numbers of CD138+CD38hi plasmablasts compared to control cells. Thus, our findings describe for the first time a functional role of SOX5 during late B cell development reducing the proliferative capacity and thus potentially affecting the differentiation of B cells during the germinal center response.
authors.affiliation: Center for Chronic Immunodeficiency (CCI), University Medical Center and University Freiburg, Freiburg, Germany.
authors.forename: Mirzokhid
authors.initials: M
authors.lastname: Rakhmanov
authors.affiliation: Center for Chronic Immunodeficiency (CCI), University Medical Center and University Freiburg, Freiburg, Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: Sic
authors.affiliation: Center for Chronic Immunodeficiency (CCI), University Medical Center and University Freiburg, Freiburg, Germany.
authors.forename: Anne-Kathrin
authors.initials: AK
authors.lastname: Kienzler
authors.affiliation: Center for Chronic Immunodeficiency (CCI), University Medical Center and University Freiburg, Freiburg, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Fischer
authors.affiliation: Center for Chronic Immunodeficiency (CCI), University Medical Center and University Freiburg, Freiburg, Germany.
authors.forename: Marta
authors.initials: M
authors.lastname: Rizzi
authors.affiliation: Center for Chronic Immunodeficiency (CCI), University Medical Center and University Freiburg, Freiburg, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Seidl
authors.affiliation: Center for Chronic Immunodeficiency (CCI), University Medical Center and University Freiburg, Freiburg, Germany.
authors.forename: Kerstina
authors.initials: K
authors.lastname: Melkaoui
authors.affiliation: Center for Chronic Immunodeficiency (CCI), University Medical Center and University Freiburg, Freiburg, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Unger
authors.affiliation: Center for Chronic Immunodeficiency (CCI), University Medical Center and University Freiburg, Freiburg, Germany.
authors.forename: Luisa
authors.initials: L
authors.lastname: Moehle
authors.affiliation: Center for Chronic Immunodeficiency (CCI), University Medical Center and University Freiburg, Freiburg, Germany.
authors.forename: Nadine E
authors.initials: NE
authors.lastname: Schmit
authors.affiliation: Center for Chronic Immunodeficiency (CCI), University Medical Center and University Freiburg, Freiburg, Germany.
authors.forename: Sachin D
authors.initials: SD
authors.lastname: Deshmukh
authors.affiliation: Department of Pneumology, University Medical Center and University Freiburg, Freiburg, Germany.
authors.forename: Cemil Korcan
authors.initials: CK
authors.lastname: Ayata
authors.affiliation: Division of Molecular Immunology, Department of Internal Medicine III, Nikolaus Fiebiger Center, University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schuh
authors.affiliation: Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: Zhibing
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: CIRI, INSERM U1111, EVIR, Ecole Normale Supérieure de Lyon, Université de Lyon, Lyon, France.
authors.forename: François-Loic
authors.initials: FL
authors.lastname: Cosset
authors.affiliation: CIRI, INSERM U1111, EVIR, Ecole Normale Supérieure de Lyon, Université de Lyon, Lyon, France; INSERM U1065, C3M, Metabolic control of cell deaths, Nice, France.
authors.forename: Els
authors.initials: E
authors.lastname: Verhoeyen
authors.affiliation: Center for Chronic Immunodeficiency (CCI), University Medical Center and University Freiburg, Freiburg, Germany; Division of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Hans-Hartmut
authors.initials: HH
authors.lastname: Peter
authors.affiliation: Center for Chronic Immunodeficiency (CCI), University Medical Center and University Freiburg, Freiburg, Germany; Division of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Reinhard E
authors.initials: RE
authors.lastname: Voll
authors.affiliation: Center for Chronic Immunodeficiency (CCI), University Medical Center and University Freiburg, Freiburg, Germany; Division of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Salzer
authors.affiliation: Center for Chronic Immunodeficiency (CCI), University Medical Center and University Freiburg, Freiburg, Germany; Division of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Eibel
authors.affiliation: Center for Chronic Immunodeficiency (CCI), University Medical Center and University Freiburg, Freiburg, Germany; Division of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Warnatz
mesh_terms: D001324:Autoantigens / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics; D010950:Plasma Cells / Q000166:cytology* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D055755:SOXD Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D001324:Autoantigens; D012333:RNA, Messenger; C491720:SOX13 protein, human; C490301:SOX5 protein, human; D055755:SOXD Transcription Factors