Precocious expression of Blimp1 in the B cell lineage causes autoimmunity
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ABSTRACT:
PROVIDER: PRJNA437913 | ENA |
REPOSITORIES: ENA
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Project description:The transcription factor Blimp1 is not only an essential regulator of plasma cells, but also a risk factor for the development of autoimmune disease. Here, we demonstrate that the mouse Prdm1 (Blimp1) gene was partially activated at the chromatin and transcription level in early B cell development, although mature Prdm1 mRNA did not accumulate due to posttranscriptional regulation. By analyzing a mouse model that facilitated ectopic Blimp1 protein expression throughout B lymphopoiesis, we could demonstrate that Blimp1 impaired B cell development by interfering with the B cell gene expression program, while leading to an increased abundance of plasma cells by promoting premature plasmablast differentiation of immature and mature B cells. With progressive age, these mice developed an autoimmune phenotype characterized by the presence of autoantibodies and glomerulonephritis. Hence, these data identified ectopic Blimp1 expression as a novel mechanism that can explain how Blimp1 as a risk factor contributes to the development of autoimmune disease.
2018-11-30 | GSE111692 | GEO
Project description:Dominant GNAI2 mutants causes human immunodeficiency and autoimmunity
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Project description:Dominant GNAI2 mutants causes human immunodeficiency and autoimmunity
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Project description:This SuperSeries is composed of the following subset Series: GSE16720: Comparison of precocious and non-precocious salmon brain GSE16721: Comparison of gene expression in the salmon parr precocious and non-precocious testis Refer to individual Series
2010-05-16 | E-GEOD-16860 | biostudies-arrayexpress
Project description:The objective was to compare gene expression in salmon precocious and non-precocious parr brain tissue. Eight microarray hybridisations were carried out in total as part of this design. To compare brain samples total RNA from 10 individual brains (dissected of hypothalamus and pituitary) of precocious fish and 10 brains of non-precocious fish were pooled to give two pools each of five precocious (PA and PB) and non-precocious (NPA and NPB) brains. Each pool of precocious brains was compared in a dye swap experiment with each pool of non-precocious brains.
2010-05-16 | E-GEOD-16720 | biostudies-arrayexpress
Project description:Antibody-secreting plasma cells are the terminal stage of the B-cell lineage. Plasma cell differentiation requires a major resetting of gene expression to silence the B cell transcriptional program, whilst establishing secretory function and long-term survival. The transcription factors Blimp1 and Irf4 are essential for the initial differentiation of activated B cells to antibody-secreting cells, however their function in mature plasma cells remains elusive. We have found that while Irf4 was essential for plasma cell survival, Blimp1 was dispensable. Blimp1-deficient cells retained the unique plasma cell transcriptional signature, but lost the ability to secrete antibody or to maintain the characteristic size and ultrastructure of plasma cells. Blimp1 was required for full expression of many components of the unfolded protein response (UPR), including Xbp1 and Atf6, as well as for the appropriate processing of Igh mRNA. The overlap of Blimp1 and Xbp1 function was restricted to the UPR genes, with Blimp1 uniquely regulating activity of the mTOR pathway, plasma cell size and morphology. These studies establish Blimp1 as a major regulator of the UPR pathway that is also required for the unique metabolic requirements of plasma cells enabling the secretion of protective antibody. RNA-seq was performed on wild type, Blimp1-/- and Xbp1-/- mouse plasma cells. Between two to four biological replicates were generated and sequenced for each sample.
2016-01-18 | E-GEOD-70981 | biostudies-arrayexpress
Project description:The objective was to compare gene expression in salmon precocious and non-precocious parr brain tissue.
2009-12-31 | GSE16720 | GEO
Project description:The objective was to compare gene expression in salmon precocious and non-precocious parr testis tissue. Nine microarray hybridisations were carried out in total as part of this loop design. Total RNA from 3 pools(PG1-PG3) each of 4 precocious fish testes were compared with 3 pools (NP1-NP3) each of 10 non-precocious fish testes. There were no direct dye swaps but there was overall dye balance in the loop
2010-05-16 | E-GEOD-16721 | biostudies-arrayexpress
Project description:Antibody-secreting plasma cells are the terminal stage of the B-cell lineage. Plasma cell differentiation requires a major resetting of gene expression to silence the B cell transcriptional program, whilst establishing secretory function and long-term survival. The transcription factors Blimp1 and Irf4 are essential for the initial differentiation of activated B cells to antibody-secreting cells, however their function in mature plasma cells remains elusive. We have found that while Irf4 was essential for plasma cell survival, Blimp1 was dispensable. Blimp1-deficient cells retained the unique plasma cell transcriptional signature, but lost the ability to secrete antibody or to maintain the characteristic size and ultrastructure of plasma cells. Blimp1 was required for full expression of many components of the unfolded protein response (UPR), including Xbp1 and Atf6, as well as for the appropriate processing of Igh mRNA. The overlap of Blimp1 and Xbp1 function was restricted to the UPR genes, with Blimp1 uniquely regulating activity of the mTOR pathway, plasma cell size and morphology. These studies establish Blimp1 as a major regulator of the UPR pathway that is also required for the unique metabolic requirements of plasma cells enabling the secretion of protective antibody.
2016-01-18 | GSE70981 | GEO