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* IFR128, Biosciences Lyon-Gerland, Institut National de la Santé et de la Recherche Médicale, Unité 404 Lyon, France;
Laboratoire de Biologie Moléculaire et Cellulaire, Unité Mixte de Recherche 5161 Centre National de la Recherche Scientifique-Ecole Normale Supérieure Lyon-Institut National de la Recherche Agronomique, Lyon, France; and
Service Commun de Cytométrie en Flux, Lyon, France
Plasma cells (PC) are the effector cells of the humoral Ab response. Unlike other dedicated secretory cells, they exist as two populations with opposite cell fates: short-lived and long-lived PC. Upon transformation they lead to an incurable neoplasia called multiple myeloma. In this study we have explored the molecular mechanism of PC death. Our data show that their apoptotic pathway is unique among other hemopoietic cells inasmuch as neither the death receptors nor the mitochondria play the central role. PC apoptosis is initiated by activation of Bax at the endoplasmic reticulum membrane and subsequent activation of the endoplasmic reticulum-associated caspase-4 before the release of mitochondrial apoptogenic factors. Together, our observations indicate that the cardinal function of PC (i.e., Ig secretion) is also the cause of their death.
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