High Levels of SOX5 Decrease Proliferative Capacity of Human B Cells, but Permit Plasmablast Differentiation

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.

目前学界对转录因子SOX5在B细胞成熟过程中的差异表达与功能机制仍知之甚少。本研究在人类B细胞中鉴定出SOX5的两种全新剪接变体（splice variants），分别编码已报道的L-SOX5B同工型（isoform），以及一种新型截短型L-SOX5F同工型（isoform）。SOX5转录本（transcripts）在B细胞分化的晚期阶段呈现高表达，包括扁桃体中的非典型记忆B细胞、活化CD21low B细胞以及生发中心（germinal center）B细胞。在扁桃体组织切片中，SOX5的表达主要定位于生发中心明区（light zone）的中心细胞（centrocytes）。体外刺激后，SOX5的表达在细胞增殖过程中被下调（down-regulated），而高表达水平则可促进浆母细胞（plasmablast）的分化。在人类原代B淋巴细胞（primary B lymphocytes）中过表达（overexpression）L-SOX5F，可导致细胞增殖能力下降、CD138neg B细胞存活率降低，但与对照组相比，CD138+CD38hi浆母细胞的数量无显著差异。综上，本研究首次阐明了SOX5在B细胞晚期发育过程中的功能作用：其可降低细胞增殖能力，进而可能影响生发中心反应中B细胞的分化进程。