scholarly journals Dickkopf-3 Acts as a Modulator of B Cell Fate and Function

2015 ◽  
Vol 194 (6) ◽  
pp. 2624-2634 ◽  
Author(s):  
Julia Ludwig ◽  
Giuseppina Federico ◽  
Sandra Prokosch ◽  
Günter Küblbeck ◽  
Sabine Schmitt ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Fate ◽  
And Function

Epigenetic regulation of B cell fate and function during an immune response

2019 ◽  
Vol 288 (1) ◽  
pp. 75-84 ◽  
Author(s):  
Yan Zhang ◽  
Kim L. Good‐Jacobson
Keyword(s):  
Immune Response ◽  
B Cell ◽  
Cell Fate ◽  
Epigenetic Regulation ◽  
And Function

Regulation and Function of NOTCH2 in B-CLL Cells.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1138-1138
Author(s):  
Rainer Hubmann ◽  
Martin Hilgarth ◽  
Susanne Schnabl ◽  
Dita Demirtas ◽  
Josef D. Schwarzmeier ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Fate ◽  
Target Gene ◽  
Active Form ◽  
Lymphocytic Leukemia ◽  
B Cell Differentiation ◽  
Cell Fate Decisions ◽  
Mutational Status ◽  
And Function

Abstract B-cell chronic lymphocytic leukemia (B-CLL) represents a clonal expansion of self-reactive CD5+ B-lymphocytes which seems to be resistant to apoptosis in vivo. One of the characteristics of B-CLL lymphocytes is the high expression of the B-cell differentiation/activation marker CD23 which we recently identified as a target gene for NOTCH2 signaling. NOTCH2 is implicated in the development/homeostasis of murine CD5+ (B-1a) B-cells, suggesting a function for human NOTCH2 in B-CLL leukemogenesis. Here we show that peripheral B-CLL lymphocytes overexpress a transcriptionally active form of NOTCH2 (N2IC) irrespective of their prognostic marker profile (ie. IgVH mutational status, CD38 expression, and cytogenetics). Although the majority of unstimulated B-CLL samples downregulate their N2IC activity in vitro, DNA-bound N2IC complexes could be maintained by the protein kinase C (PKC) activator TPA (12-O-tetradecanoylphorbol 13-acetate) accompanied by an upregulation of the NOTCH2 target gene CD23 and increased B-CLL cell viability. These effects are sensitive to the PKC-δ selective inhibitor Rottlerin. In 80% of B-CLL cases, NOTCH2 signaling was found to be resistant to the γ-secretase inhibitors (GSI’s) Dapt and compound E, indicative for the expression of truncated forms of NOTCH2 which do not require γ-secretase for processing and function. Inhibition of NOTCH2 either by Dapt in GSI sensitive B-CLL cases or, more specifically, by RNA interference downregulates CD23 expression on the mRNA and protein level and sensitizes B-CLL cells for apoptosis. Since self-reactive B-cells are normally eliminated either by chronic (anergy) or apoptotic (negative selection) B-cell receptor (BCR) signaling, we asked whether NOTCH2 modulates B-cell fate decisions triggered by the BCR. For this reason, we stably transduced the human B-cell line BL41 with constitutive active forms of NOTCH2 and found that NOTCH2 inhibits BCR mediated apoptosis induced by surface-IgM cross-linking. In summary, the data demonstrate that NOTCH2 signaling is deregulated in B-CLL cells and might be critically involved in the PKC-dependent maintenance of their malignant phenotype.

scholarly journals Regulation of B cell fate, survival, and function by mitochondria and autophagy

Mitochondrion ◽  
2018 ◽  
Vol 41 ◽  
pp. 58-65 ◽  
Author(s):  
Hector Sandoval ◽  
Srikanth Kodali ◽  
Jin Wang
Keyword(s):  
B Cell ◽  
Cell Fate ◽  
And Function

The roles of STAT6 in regulating B cell fate, activation, and function

2021 ◽  
Vol 233 ◽  
pp. 87-91
Author(s):  
Wei Wang ◽  
Luman Wang ◽  
Bingbing Zha
Keyword(s):  
B Cell ◽  
Cell Fate ◽  
And Function

scholarly journals Phosphatidylcholine as a metabolic cue for determining B cell fate and function

2016 ◽  
Vol 310 ◽  
pp. 78-88 ◽  
Author(s):  
Joseph W. Brewer ◽  
Viktoriya Solodushko ◽  
Ileana Aragon ◽  
Robert A. Barrington
Keyword(s):  
B Cell ◽  
Cell Fate ◽  
And Function

scholarly journals TGFβ Superfamily Members as Regulators of B Cell Development and Function—Implications for Autoimmunity

2018 ◽  
Vol 19 (12) ◽  
pp. 3928 ◽  
Author(s):  
Esther Tamayo ◽  
Pilar Alvarez ◽  
Ramón Merino
Keyword(s):  
B Cell ◽  
Cell Fate ◽  
Cell Development ◽  
B Cell Development ◽  
Postnatal Life ◽  
Potential Contribution ◽  
Cellular Processes ◽  
New Findings ◽  
And Function ◽  
Tgfβ Superfamily

The TGFβ superfamily is composed of more than 33 growth and differentiation factors, including TGFβ1, β2, β3, BMPs, GDFs, nodal-related proteins, and activins. These members usually exert pleiotropic actions on several tissues and control multiple cellular processes, such as cell growth, cell survival, cell migration, cell fate specification, and differentiation, both during embryonic development and postnatal life. Although the effects of these factors on immune responses were elucidated long ago, most studies have been focused on the actions of TGFβs on T cells, as major regulators of adaptive immunity. In this review, we discuss new findings about the involvement of TGFβ superfamily members in the control of B cell development and function. Moreover, the potential contribution of TGFβ signaling to control B cell-mediated autoimmune diseases and its utility in the design of new therapies are also discussed.

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