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

Rakhmanov M, Sic H, Kienzler AK, Fischer B, Rizzi M, Seidl M, Melkaoui K, Unger S, Moehle L, Schmit NE, Deshmukh SD, Ayata CK, Schuh W, Zhang Z, Cosset FL, Verhoeyen E, Peter HH, Voll RE, Salzer U, Eibel H, Warnatz K

PLoS ONE 2014;9(6):e100328

Abstract

PMID: 24945754

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.