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：Adem Jemal^*; Hamalainen Aleksi; Ropponen Antti; Eeva Jonna; Eray Mine; Nuutinen Ulla; Pelkonen Jukka

来源：Molecular Immunology, 2015, 67(2): 240-247.

DOI：10.1016/j.molimm.2015.05.017

• ERK1/2
• BCR
• CD40
• Bcl-2 family proteins
• Germinal center

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 Bc1-xL in BCR-primed HF1A3 GC B cells. In conclusion, MEK-ERK pathway and Bc1-2 family proteins are crucial players in BCR-mediated survival/apoptosis and CD40-mediated survival.

• 出版日期2015-10