ERK1/2 has an essential role in B cell receptor- and CD40-induced signaling in an in vitro model of germinal center B cell selection.

作者信息

Adem Jemal, Hämäläinen Aleksi, Ropponen Antti, Eeva Jonna, Eray Mine, Nuutinen Ulla, Pelkonen Jukka

机构信息

Department of Clinical Microbiology, Institute of Clinical Medicine, University of Eastern Finland, Yliopistonranta 1 C, 70210 Kuopio, Finland; Cancer Center of University of Eastern, Kuopio, Finland.

Department of Clinical Microbiology, Institute of Clinical Medicine, University of Eastern Finland, Yliopistonranta 1 C, 70210 Kuopio, Finland.

出版信息

Mol Immunol. 2015 Oct;67(2 Pt B):240-7. doi: 10.1016/j.molimm.2015.05.017. Epub 2015 Jun 6.

DOI:10.1016/j.molimm.2015.05.017

PMID:26054744

Abstract

Germinal center (GC) B cells undergo apoptosis after B cell receptor (BCR) ligation, unless they receive CD40-mediated survival signal from helper T cells. In the present study, we used a human follicular lymphoma cell line HF1A3, as an in vitro model to study the selection process in germinal centers. We show here that BCR ligation led to immediate ERK1/2 activation and phosphorylations of its downstream targets, Bim EL/L and Bcl-2 (at Ser70) which resulted in short-term survival. On the other hand, during the late phase of BCR signaling, ERK1/2 phosphorylation was inhibited which resulted in apoptosis. In addition, CD40 signaling led to sustained ERK1/2 activation and up-regulation of Bcl-xL in BCR-primed HF1A3 GC B cells. In conclusion, MEK-ERK pathway and Bcl-2 family proteins are crucial players in BCR-mediated survival/apoptosis and CD40-mediated survival.

摘要