title: CHOP-independent apoptosis and pathway-selective induction of the UPR in developing plasma cells.
abstract: Upon antigen stimulation, B lymphocytes differentiate into antibody secreting cells (ASC), most of which undergo apoptosis after a few days of intense Ig production. Differentiation entails expansion of the endoplasmic reticulum (ER) and requires XBP1 but not other elements of the unfolded protein response, like PERK. Moreover, normal and malignant ASC are exquisitely sensitive to proteasome inhibitors, but the underlying mechanisms are poorly understood. Here we analyze the role of C/EBP homologous protein (CHOP), a transcription factor mediating apoptosis in many cell types that experience high levels of ER stress. CHOP is transiently induced early upon B cell stimulation: covalent IgM aggregates form more readily and IgM secretion is slower in chop(-/-) cells. Despite these subtle changes, ASC differentiation and lifespan are normal in chop(-/-) mice. Unlike fibroblasts and other cell types, chop(-/-) ASC are equally or slightly more sensitive to proteasome inhibitors and ER stressors, implying tissue-specific roles for CHOP in differentiation and stress.
authors.affiliation: Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Masciarelli
authors.forename: Anna M
authors.initials: AM
authors.lastname: Fra
authors.forename: Niccolò
authors.initials: N
authors.lastname: Pengo
authors.forename: Milena
authors.initials: M
authors.lastname: Bertolotti
authors.forename: Simone
authors.initials: S
authors.lastname: Cenci
authors.forename: Claudio
authors.initials: C
authors.lastname: Fagioli
authors.forename: David
authors.initials: D
authors.lastname: Ron
authors.forename: Linda M
authors.initials: LM
authors.lastname: Hendershot
authors.forename: Roberto
authors.initials: R
authors.lastname: Sitia
mesh_terms: D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D007075:Immunoglobulin M / Q000378:metabolism; D051379:Mice; D010950:Plasma Cells / Q000166:cytology* / Q000378:metabolism*; D015398:Signal Transduction; D013312:Stress, Physiological; D051742:Transcription Factor CHOP / Q000172:deficiency / Q000378:metabolism*; D056811:Unfolded Protein Response
chemical_list: D007075:Immunoglobulin M; D051742:Transcription Factor CHOP