Prostaglandin E 2 -Induced AKT Activation Regulates the Life Span of Short-Lived Plasma Cells by Attenuating IRE1α Hyperactivation.

The mechanism regulating the life span of short-lived plasma cells (SLPCs) remains poorly understood. Here we demonstrated that the EP4-mediated activation of AKT by PGE ₂ was required for the proper control of inositol-requiring transmembrane kinase endoribonuclease-1α (IRE1α) hyperactivation and hence the endoplasmic reticulum (ER) homeostasis in IgM-producing SLPCs. Disruption of the PGE ₂ -EP4-AKT signaling pathway resulted in IRE1α-induced activation of JNK, leading to accelerated death of SLPCs. Consequently, Ptger4 -deficient mice (C57BL/6) exhibited a markedly impaired IgM response to T-independent Ags and increased susceptibility to Streptococcus pneumoniae infection. This study reveals a highly selective impact of the PGE ₂ -EP4 signal on the humoral immunity and provides a link between ER stress response and the life span of SLPCs.
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