title: Autophagy, a new determinant of plasma cell differentiation and antibody responses.
abstract: Plasma cells, the terminal effectors of the B lymphoid lineage, are responsible for the humoral arm of adaptive immunity. Their differentiation from B cells entails a profound cellular reshaping inherently associated with stress. Autophagy is a conserved adaptive cellular strategy recently implicated in differentiation and immunity. We identified a novel autophagic function in plasma cells. Autophagy restricts the expression of the transcriptional repressor Blimp-1 and immunoglobulins through a selective negative control on the endoplasmic reticulum and its stress signaling response, thereby optimizing energy and viability. As a result, autophagy in vivo sustains antibody responses, and is an essential intrinsic determinant of the bone marrow long-lived plasma cell niche. Here, I discuss several immune and biomedical implications, and experimental issues to be addressed in the near future.
authors.affiliation: Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milano, Italy; Università Vita-Salute San Raffaele, Milano, Italy; Bone Pathophysiology Program (BoNetwork), Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milano, Italy. Electronic address: cenci.simone@hsr.it.
authors.forename: Simone
authors.initials: S
authors.lastname: Cenci
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D001343:Autophagy / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology*; D006801:Humans; D010950:Plasma Cells / Q000276:immunology*
keywords: Antibody; Atg5; Autophagy; B cell; Blimp-1; ER-phagy; Endoplasmic reticulum; Immunological memory; Multiple myeloma; Plasma cell; Proteostasis; Reticulophagy; Ubiquitin; Unfolded protein response; XBP-1