title: The specialized unfolded protein response of B lymphocytes: ATF6α-independent development of antibody-secreting B cells.
abstract: B lymphocytes, like all mammalian cells, are equipped with the unfolded protein response (UPR), a complex signaling system allowing for both pro- and mal-adaptive responses to increased demands on the endoplasmic reticulum (ER). The UPR is comprised of three signaling pathways initiated by the ER transmembrane stress sensors, IRE1α/β, PERK and ATF6α/β. Activation of IRE1 yields XBP1(S), a transcription factor that directs expansion of the ER and enhances protein biosynthetic and secretory machinery. XBP1(S) is essential for the differentiation of B lymphocytes into antibody-secreting cells. In contrast, the PERK pathway, a regulator of translation and transcription, is dispensable for the generation of antibody-secreting cells. Functioning as a transcription factor, ATF6α can augment ER quality control processes and drive ER expansion, but the potential role of this UPR pathway in activated B cells has not been investigated. Here, we report studies of ATF6α-deficient B cells demonstrating that ATF6α is not required for the development of antibody-secreting cells. Thus, when B cells are stimulated to secrete antibody, a specialized UPR relies exclusively on the IRE1-XBP1 pathway to remodel the ER and expand cellular secretory capacity.
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, University of South Alabama, 5851 USA Drive North, Mobile, AL 36688, United States.
authors.forename: Ileana V
authors.initials: IV
authors.lastname: Aragon
authors.forename: Robert A
authors.initials: RA
authors.lastname: Barrington
authors.forename: Suzanne
authors.initials: S
authors.lastname: Jackowski
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Mori
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Brewer
mesh_terms: D051702:Activating Transcription Factor 6 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D000921:Antibody-Producing Cells / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000071701:Regulatory Factor X Transcription Factors; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D056811:Unfolded Protein Response; D000071717:X-Box Binding Protein 1; D019892:eIF-2 Kinase / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D051702:Activating Transcription Factor 6; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D017346:Protein Serine-Threonine Kinases; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; D019892:eIF-2 Kinase; C497112:Atf6 protein, mouse; C000605544:Xbp1 protein, mouse; C486556:Ern2 protein, mouse