scholarly journals Genome-wide Analysis of HDAC Inhibitor-mediated Modulation of microRNAs and mRNAs in B Cells Induced to Undergo Class-switch DNA Recombination and Plasma Cell Differentiation

10.3791/55135 ◽  
2017 ◽  
Author(s):  
Helia N. Sanchez ◽  
Tian Shen ◽  
Dawn Garcia ◽  
Zhao Lai ◽  
Paolo Casali ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
B Cells ◽  
Plasma Cell ◽  
Hdac Inhibitor ◽  
Dna Recombination ◽  
Plasma Cell Differentiation ◽  
Genome Wide Analysis ◽  
Class Switch ◽  
Genome Wide ◽  
Class Switch Dna Recombination

Genomic deletion of the whole IgH 3′ regulatory region (hs3a, hs1,2, hs3b, and hs4) dramatically affects class switch recombination and Ig secretion to all isotypes

Blood ◽  
2010 ◽  
Vol 116 (11) ◽  
pp. 1895-1898 ◽  
Author(s):  
Christelle Vincent-Fabert ◽  
Remi Fiancette ◽  
Eric Pinaud ◽  
Véronique Truffinet ◽  
Nadine Cogné ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
B Cells ◽  
Plasma Cell ◽  
Regulatory Region ◽  
Class Switch Recombination ◽  
B Cell Differentiation ◽  
Plasma Cell Differentiation ◽  
Heavy Chains ◽  
Class Switch ◽  
Transcriptional Changes

Abstract The immunoglobulin heavy chain locus (IgH) undergoes multiple changes along B-cell differentiation. In progenitor B cells, V(D)J assembly allows expression of μ heavy chains. In mature B cells, class switch recombination may replace the expressed constant (C)μ gene with a downstream CH gene. Finally, plasma cell differentiation strongly boosts IgH transcription. How the multiple IgH transcriptional enhancers tune these changes is unclear. Here we demonstrate that deletion of the whole IgH 3′ regulatory region (3′RR) allows normal maturation until the stage of IgM/IgD expressing lymphocytes, but nearly abrogates class switch recombination to all CH genes. Although plasma cell numbers are unaffected, we reveal the role of the 3′RR into the transcriptional burst normally associated with plasma cell differentiation. Our study shows that transcriptional changes and recombinations occurring after antigen-encounter appear mainly controlled by the 3′RR working as a single functional unit.

scholarly journals The transcription factors IRF8 and PU.1 negatively regulate plasma cell differentiation

2014 ◽  
Vol 211 (11) ◽  
pp. 2169-2181 ◽  
Author(s):  
Sebastian Carotta ◽  
Simon N. Willis ◽  
Jhagvaral Hasbold ◽  
Michael Inouye ◽  
Swee Heng Milon Pang ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Cell Differentiation ◽  
B Cells ◽  
B Cell ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Terminal Differentiation ◽  
Plasma Cell Differentiation ◽  
Class Switch ◽  
Complex Functions

Activated B cells undergo immunoglobulin class-switch recombination (CSR) and differentiate into antibody-secreting plasma cells. The distinct transcriptomes of B cells and plasma cells are maintained by the antagonistic influences of two groups of transcription factors: those that maintain the B cell program, including BCL6 and PAX5, and plasma cell–promoting factors, such as IRF4 and BLIMP-1. We show that the complex of IRF8 and PU.1 controls the propensity of B cells to undergo CSR and plasma cell differentiation by concurrently promoting the expression of BCL6 and PAX5 and repressing AID and BLIMP-1. As the PU.1–IRF8 complex functions in a reciprocal manner to IRF4, we propose that concentration-dependent competition between these factors controls B cell terminal differentiation.

Heme regulates B-cell differentiation, antibody class switch, and heme oxygenase-1 expression in B cells as a ligand of Bach2

Blood ◽  
2011 ◽  
Vol 117 (20) ◽  
pp. 5438-5448 ◽  
Author(s):  
Miki Watanabe-Matsui ◽  
Akihiko Muto ◽  
Toshitaka Matsui ◽  
Ari Itoh-Nakadai ◽  
Osamu Nakajima ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
B Cells ◽  
B Cell ◽  
Heme Oxygenase ◽  
Plasma Cell ◽  
Heme Oxygenase 1 ◽  
Plasma Cell Differentiation ◽  
Class Switch ◽  
Antibody Class

Abstract Heme binds to proteins to modulate their function, thereby functioning as a signaling molecule in a variety of biologic events. We found that heme bound to Bach2, a transcription factor essential for humoral immunity, including antibody class switch. Heme inhibited the DNA binding activity of Bach2 in vitro and reduced its half-life in B cells. When added to B-cell primary cultures, heme enhanced the transcription of Blimp-1, the master regulator of plasma cells, and skewed plasma cell differentiation toward the IgM isotype, decreasing the IgG levels in vitro. Intraperitoneal injection of heme in mice inhibited the production of antigen-specific IgM when heme was administered simultaneously with the antigen but not when it was administered after antigen exposure, suggesting that heme also modulates the early phase of B-cell responses to antigen. Heme oxygenase-1, which is known to be regulated by heme, was repressed by both Bach2 and Bach1 in B cells. Furthermore, the expression of genes for heme uptake changed in response to B-cell activation and heme administration. Our results reveal a new function for heme as a ligand of Bach2 and as a modulatory signal involved in plasma cell differentiation.

scholarly journals Down-regulation of BLIMP1α by the EBV oncogene, LMP-1, disrupts the plasma cell differentiation program and prevents viral replication in B cells: implications for the pathogenesis of EBV-associated B-cell lymphomas

Blood ◽  
2011 ◽  
Vol 117 (22) ◽  
pp. 5907-5917 ◽  
Author(s):  
Katerina Vrzalikova ◽  
Martina Vockerodt ◽  
Sarah Leonard ◽  
Andrew Bell ◽  
Wenbin Wei ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
B Cells ◽  
B Cell ◽  
Virus Replication ◽  
Plasma Cell ◽  
Germinal Center ◽  
Lytic Cycle ◽  
Transformed Cells ◽  
Down Regulation ◽  
Plasma Cell Differentiation

AbstractAn important pathogenic event in Epstein-Barr virus (EBV)-associated lymphomas is the suppression of virus replication, which would otherwise lead to cell death. Because virus replication in B cells is intimately linked to their differentiation toward plasma cells, we asked whether the physiologic signals that drive normal B-cell differentiation are absent in EBV-transformed cells. We focused on BLIMP1α, a transcription factor that is required for plasma cell differentiation and that is inactivated in diffuse large B-cell lymphomas. We show that BLIMP1α expression is down-regulated after EBV infection of primary germinal center B cells and that the EBV oncogene, latent membrane protein-1 (LMP-1), is alone capable of inducing this down-regulation in these cells. Furthermore, the down-regulation of BLIMP1α by LMP-1 was accompanied by a partial disruption of the BLIMP1α transcriptional program, including the aberrant induction of MYC, the repression of which is required for terminal differentiation. Finally, we show that the ectopic expression of BLIMP1α in EBV-transformed cells can induce the viral lytic cycle. Our results suggest that LMP-1 expression in progenitor germinal center B cells could contribute to the pathogenesis of EBV-associated lymphomas by down-regulating BLIMP1α, in turn preventing plasma cell differentiation and induction of the viral lytic cycle.

scholarly journals TLR9 Signaling Suppresses the Canonical Plasma Cell Differentiation Program in Follicular B Cells

2018 ◽  
Vol 9 ◽  
Author(s):  
Bárbara José Antunes Baptista ◽  
Alessandra Granato ◽  
Fábio B. Canto ◽  
Fabricio Montalvão ◽  
Lucas Tostes ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
B Cells ◽  
Plasma Cell ◽  
Plasma Cell Differentiation ◽  
Follicular B Cells ◽  
Tlr9 Signaling

scholarly journals Intrinsic Plasma Cell Differentiation Defects in B Cell Expansion with NF-κB and T Cell Anergy Patient B Cells

2017 ◽  
Vol 8 ◽  
Author(s):  
Swadhinya Arjunaraja ◽  
Brent D. Nosé ◽  
Gauthaman Sukumar ◽  
Nathaniel M. Lott ◽  
Clifton L. Dalgard ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Plasma Cell ◽  
Cell Expansion ◽  
Plasma Cell Differentiation ◽  
T Cell Anergy ◽  
Cell Anergy

scholarly journals IL‐6 Triggers IL‐21 production by human CD4 + T cells to drive STAT3‐dependent plasma cell differentiation in B cells

2012 ◽  
Vol 90 (8) ◽  
pp. 802-811 ◽  
Author(s):  
Sean A Diehl ◽  
Heike Schmidlin ◽  
Maho Nagasawa ◽  
Bianca Blom ◽  
Hergen Spits
Keyword(s):  
T Cells ◽  
Cell Differentiation ◽  
B Cells ◽  
Plasma Cell ◽  
Cd4 T Cells ◽  
Plasma Cell Differentiation
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