title: High rate of antibody secretion is not integral to plasma cell differentiation as revealed by XBP-1 deficiency.
abstract: During B cell terminal differentiation, a complex set of transcription factors interact to drive the phenotypic and functional changes leading to the development of Ab-secreting cells (ASCs). The transcription factor X-box binding protein 1 (XBP-1) is an essential part of one of the branches of the unfolded protein response (UPR). The UPR is induced when a cell has to handle large amounts of proteins, as is the case in ASCs. Although XBP-1 was initially also ascribed an indispensable function in plasma cell development, later studies of B cell-specific deletion reported a much milder consequence of XBP-1 deficiency. Our interest was to determine whether XBP-1 was integral for the differentiation of plasma cells. Using both in vitro and in vivo assays, we found efficient generation of ASCs in the absence of XBP-1. ASCs were present at normal frequencies in resting and immunized mice and displayed a pattern of surface markers typical for plasma cells. The absence of XBP-1 resulted in a reduction but not ablation of Ab secretion and the failure to develop the cellular morphology characteristic of ASCs. Thus, XBP-1 deficiency demonstrates that the gene regulatory program controlling plasma cell differentiation can proceed relatively normally in the absence of high rates of Ig secretion.
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia.
authors.forename: Nadine
authors.initials: N
authors.lastname: Taubenheim
authors.forename: David M
authors.initials: DM
authors.lastname: Tarlinton
authors.forename: Simon
authors.initials: S
authors.lastname: Crawford
authors.forename: Lynn M
authors.initials: LM
authors.lastname: Corcoran
authors.forename: Philip D
authors.initials: PD
authors.lastname: Hodgkin
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Nutt
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000276:immunology / Q000378:metabolism; D015322:Gene Rearrangement, B-Lymphocyte / Q000276:immunology; D007136:Immunoglobulins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors / Q000172:deficiency* / Q000276:immunology / Q000378:metabolism; D000071717:X-Box Binding Protein 1
chemical_list: D004268:DNA-Binding Proteins; D007136:Immunoglobulins; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605544:Xbp1 protein, mouse