High levels of SOX5 decrease proliferative capacity of human B cells, but permit plasmablast differentiation

• Published in: PloS one Vol. 9; no. 6; p. e100328
• Main Authors: Rakhmanov, Mirzokhid, Sic, Heiko, Kienzler, Anne-Kathrin, Fischer, Beate, Rizzi, Marta, Seidl, Maximilian, Melkaoui, Kerstina, Unger, Susanne, Moehle, Luisa, Schmit, Nadine E, Deshmukh, Sachin D, Ayata, Cemil Korcan, Schuh, Wolfgang, Zhang, Zhibing, Cosset, François-Loic, Verhoeyen, Els, Peter, Hans-Hartmut, Voll, Reinhard E, Salzer, Ulrich, Eibel, Hermann, Warnatz, Klaus
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 19-06-2014; Public Library of Science (PLoS)
• Subjects: Alternative splicing; Autoantigens - genetics; Autoantigens - metabolism; Bacteriology; Biology and Life Sciences; Cell cycle; Cell differentiation; Cell Differentiation - genetics; Cell Line, Tumor; Cell Proliferation; Cell survival; Cells, Cultured; Differentiation (biology); Gene expression; Gene Expression Regulation; Humans; Immunological memory; Immunology; Life Sciences; Lymphocyte Activation - genetics; Lymphocytes; Lymphocytes B; Medicine and Health Sciences; Memory cells; Microbiology and Parasitology; Neurogenesis; Plasma Cells - cytology; Plasma Cells - metabolism; Proteins; Rheumatology; RNA, Messenger - genetics; RNA, Messenger - metabolism; SOXD Transcription Factors - genetics; SOXD Transcription Factors - metabolism; Tonsil; Transcription factors; Virology; Cell Line; Cell Proliferation; RNA; Lymphocyte Activation; Humans; Gene Expression Regulation; Autoantigens; SOXD Transcription Factors; Messenger; Cells; Tumor; Cell Differentiation; Cultured; Plasma Cells
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0100328

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.