Faculty Opinions recommendation of The B-cell identity factor Pax5 regulates distinct transcriptional programmes in early and late B lymphopoiesis.

2012 ◽  
Author(s):  
E Charles Snow
Keyword(s):  
B Cell ◽  
B Lymphopoiesis ◽  
Cell Identity

scholarly journals The B-cell identity factor Pax5 regulates distinct transcriptional programmes in early and late B lymphopoiesis

2012 ◽  
Vol 31 (14) ◽  
pp. 3130-3146 ◽  
Author(s):  
Roger Revilla-i-Domingo ◽  
Ivan Bilic ◽  
Bojan Vilagos ◽  
Hiromi Tagoh ◽  
Anja Ebert ◽  
...  
Keyword(s):  
B Cell ◽  
B Lymphopoiesis ◽  
Cell Identity

scholarly journals The influence of space and time on the establishment of B cell identity

2019 ◽  
Vol 42 (4) ◽  
pp. 209-217 ◽  
Author(s):  
Ramy Elsaid ◽  
Junjie Yang ◽  
Ana Cumano
Keyword(s):  
B Cell ◽  
Cell Identity ◽  
Space And Time

scholarly journals Ligand-independent Signaling Functions for the B Lymphocyte Antigen Receptor and Their Role in Positive Selection during B Lymphopoiesis

2001 ◽  
Vol 194 (11) ◽  
pp. 1583-1596 ◽  
Author(s):  
Gregory Bannish ◽  
Ezequiel M. Fuentes-Pananá ◽  
John C. Cambier ◽  
Warren S. Pear ◽  
John G. Monroe
Keyword(s):  
B Cells ◽  
B Cell ◽  
B Lymphocyte ◽  
Antigen Receptor ◽  
Cell Development ◽  
B Cell Development ◽  
B Lymphopoiesis ◽  
Biologically Relevant ◽  
Developmental Progression

Signal transduction through the B cell antigen receptor (BCR) is determined by a balance of positive and negative regulators. This balance is shifted by aggregation that results from binding to extracellular ligand. Aggregation of the BCR is necessary for eliciting negative selection or activation by BCR-expressing B cells. However, ligand-independent signaling through intermediate and mature forms of the BCR has been postulated to regulate B cell development and peripheral homeostasis. To address the importance of ligand-independent BCR signaling functions and their regulation during B cell development, we have designed a model that allows us to isolate the basal signaling functions of immunoglobulin (Ig)α/Igβ-containing BCR complexes from those that are dependent upon ligand-mediated aggregation. In vivo, we find that basal signaling is sufficient to facilitate pro-B → pre-B cell transition and to generate immature/mature peripheral B cells. The ability to generate basal signals and to drive developmental progression were both dependent on plasma membrane association of Igα/Igβ complexes and intact immunoregulatory tyrosine activation motifs (ITAM), thereby establishing a correlation between these processes. We believe that these studies are the first to directly demonstrate biologically relevant basal signaling through the BCR where the ability to interact with both conventional as well as nonconventional extracellular ligands is eliminated.

scholarly journals TP53INP1 deficiency maintains murine B lymphopoiesis in aged bone marrow through redox-controlled IL-7R/STAT5 signaling

2018 ◽  
Vol 116 (1) ◽  
pp. 211-216 ◽  
Author(s):  
Bochra Zidi ◽  
Christelle Vincent-Fabert ◽  
Laurent Pouyet ◽  
Marion Seillier ◽  
Amelle Vandevelde ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
Immune Cell ◽  
B Lymphopoiesis ◽  
Hematopoietic Stem ◽  
Chronic Oxidative Stress ◽  
The Impact ◽  
Deficient Mice

Bone marrow (BM) produces all blood and immune cells deriving from hematopoietic stem cells (HSCs). The decrease of immune cell production during aging is one of the features of immunosenescence. The impact of redox dysregulation in BM aging is still poorly understood. Here we use TP53INP1-deficient (KO) mice endowed with chronic oxidative stress to assess the influence of aging-associated redox alterations in BM homeostasis. We show that TP53INP1 deletion has no impact on aging-related accumulation of HSCs. In contrast, the aging-related contraction of the lymphoid compartment is mitigated in TP53INP1 KO mice. B cells that accumulate in old KO BM are differentiating cells that can mature into functional B cells. Importantly, this phenotype results from B cell-intrinsic events associated with defective redox control. Finally, we show that oxidative stress in aged TP53INP1-deficient mice maintains STAT5 expression and activation in early B cells, driving high Pax5 expression, which provides a molecular mechanism for maintenance of B cell development upon aging.

scholarly journals Repression of the B cell identity factor Pax5 is not required for plasma cell development

2020 ◽  
Vol 217 (11) ◽  
Author(s):  
Grace J. Liu ◽  
Markus Jaritz ◽  
Miriam Wöhner ◽  
Benedikt Agerer ◽  
Andreas Bergthaler ◽  
...  
Keyword(s):  
B Cell ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Cell Development ◽  
Transcriptional Networks ◽  
Cell Fates ◽  
Cell Identity ◽  
Cell Expression ◽  
Expression Program ◽  
Antibody Secretion

B cell and plasma cell fates are controlled by different transcriptional networks, as exemplified by the mutually exclusive expression and cross-antagonism of the B cell identity factor Pax5 and the plasma cell regulator Blimp1. It has been postulated that repression of Pax5 by Blimp1 is essential for plasma cell development. Here, we challenged this hypothesis by analyzing the IghPax5/+ mouse, which expressed a Pax5 minigene from the immunoglobulin heavy-chain locus. Despite high Pax5 expression, plasma cells efficiently developed in young IghPax5/+ mice at steady state and upon immunization, while their number moderately declined in older mice. Although Pax5 significantly deregulated the plasma cell expression program, key plasma cell regulators were normally expressed in IghPax5/+ plasma cells. While IgM and IgA secretion by IghPax5/+ plasma cells was normal, IgG secretion was modestly decreased. Hence, Pax5 repression is not essential for robust plasma cell development and antibody secretion, although it is required for optimal IgG production and accumulation of long-lived plasma cells.

Human SLP-65 isoforms contribute differently to activation and apoptosis of B lymphocytes

Blood ◽  
2006 ◽  
Vol 108 (12) ◽  
pp. 3761-3768 ◽  
Author(s):  
Annika Grabbe ◽  
Jürgen Wienands
Keyword(s):  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Adaptor Protein ◽  
Sh2 Domain ◽  
Binding Motif ◽  
B Lymphopoiesis ◽  
Suppressor Activity ◽  
B Cell Signaling ◽  
Tumor Suppressor Activity ◽  
Mitogen Activated Protein

AbstractThe SH2 domain-containing leukocyte adaptor protein of 65 kDa (SLP-65) is the key effector for signaling downstream of the B-cell antigen receptor (BCR). SLP-65 controls not only B lymphopoiesis and humoral immunity but also possesses a yet poorly defined tumor suppressor activity that is lost in many cases of acute lymphoblastic leukemia. We found that the 2 isoforms of human SLP-65 are differentially involved in positive and negative B-cell signaling. Reconstitution experiments revealed that an atypical SH3 domain-binding motif, which is present in the long but not in the short SLP-65 isoform, mediates association to Grb2 and suppresses activation of mitogen-activated protein kinases p38 and JNK as well as up-regulation of c-Fos expression. In turn, the short isoform activates not only AP1-driven but also NF-κB–driven gene transcription more potently than the long isoform. Conversely, the long rather than the short SLP-65 isoform promotes BCR-induced B-cell apoptosis. Our data further delineate the structural requirements of positive and negative SLP-65 signal transduction in normal and neoplastic cells.

Abstract 1124: Transcriptional control of B cell identity restricts metabolic fitness in human leukemia

2015 ◽  
Author(s):  
Lai N. Chan ◽  
Daniel Braas ◽  
Christian Hurtz ◽  
Seyedmehdi Shojaee ◽  
Huimin Geng ◽  
...  
Keyword(s):  
B Cell ◽  
Transcriptional Control ◽  
Human Leukemia ◽  
Cell Identity ◽  
Metabolic Fitness

scholarly journals Regulated Expression of the Eph-Related Receptor Tyrosine Kinase Hek11 in Early Human B Lymphopoiesis

Blood ◽  
1997 ◽  
Vol 90 (9) ◽  
pp. 3613-3622 ◽  
Author(s):  
Hans-Christian Aasheim ◽  
Leon W.M.M. Terstappen ◽  
Ton Logtenberg
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
Expression Patterns ◽  
B Lymphopoiesis ◽  
Fetal Bone ◽  
Degenerate Oligonucleotide ◽  
Regulated Expression ◽  
B Lineage ◽  
B Lineage Cells

Abstract Members of the large Eph family of receptor tyrosine kinases (RTKs) display temporally and spatially restricted expression patterns during embryogenesis, suggesting a role in various developmental processes. We have begun to investigate the expression of members of this receptor family during human hematopoiesis, in particular B lymphopoiesis. Expression of Eph RTKs in cells of the B-lymphoid lineage was assessed by using degenerate oligonucleotide primers based on stretches of conserved nucleic acid sequences in members of the Eph family. First, the content of Eph-family RTKs was assessed in freshly sorted fetal bone marrow pro–B cells. This population was found to harbor transcripts of the Hek8 and Hek11 members of this gene family. Subsequent analysis of expression of these genes in B cells representing various differentiation and ontogenic stages showed that the Hek8 transcript is constitutively present in all fetal and adult B-lineage cells, with high levels of expression in peripheral blood B cells. In contrast, the Hek11 transcript was exclusively found in fetal bone marrow pro–B cells and pre–B cells, but not in more mature fetal B-lineage cells. All adult B-lineage cells, from early pro–B cells to end-stage plasma cells, lacked Hek11 transcripts. The developmentally regulated expression of Hek11 during fetal B lymphopoiesis suggests a role for this gene in pre/pro–B cell expansion and/or differentiation and defines a difference in progenitor B cell populations isolated from fetal versus adult human bone marrow.

scholarly journals Early B Cell Factor Promotes B Lymphopoiesis with Reduced Interleukin 7 Responsiveness in the Absence of E2A

2004 ◽  
Vol 199 (12) ◽  
pp. 1689-1700 ◽  
Author(s):  
Christopher S. Seet ◽  
Rachel L. Brumbaugh ◽  
Barbara L. Kee
Keyword(s):  
Transcription Factors ◽  
B Cell ◽  
B Lymphopoiesis ◽  
Protein Activity ◽  
E Proteins ◽  
Helix Loop Helix ◽  
Interleukin 7 ◽  
E Protein ◽  
B Lineage ◽  
Early B Cell Factor

The basic helix-loop-helix transcription factors encoded by the E2A gene function at the apex of a transcriptional hierarchy involving E2A, early B cell factor (EBF), and Pax5, which is essential for B lymphopoiesis. In committed B lineage progenitors, E2A proteins have also been shown to regulate many lineage-associated genes. Herein, we demonstrate that the block in B lymphopoiesis imposed by the absence of E2A can be overcome by expression of EBF, but not Pax5, indicating that EBF is the essential target of E2A required for development of B lineage progenitors. Our data demonstrate that EBF, in synergy with low levels of alternative E2A-related proteins (E proteins), is sufficient to promote expression of most B lineage genes. Remarkably, however, we find that E2A proteins are required for interleukin 7–dependent proliferation due, in part, to a role for E2A in optimal expression of N-myc. Therefore, high levels of E protein activity are essential for the activation of EBF and N-myc, whereas lower levels of E protein activity, in synergy with other B lineage transcription factors, are sufficient for expression of most B lineage genes.

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