scholarly journals The Dynamics of Protein Kinase B Regulation during B Cell Antigen Receptor Engagement

1999 ◽  
Vol 145 (7) ◽  
pp. 1511-1520 ◽  
Author(s):  
Emmanuelle Astoul ◽  
Sandra Watton ◽  
Doreen Cantrell
Keyword(s):  
Plasma Membrane ◽  
B Cells ◽  
Protein Kinase ◽  
B Cell ◽  
B Lymphocytes ◽  
Protein Kinase B ◽  
B Cell Antigen Receptor ◽  
Cell Antigen Receptor ◽  
Cell Antigen ◽  
Sustained Activation

This study has used biochemistry and real time confocal imaging of green fluorescent protein (GFP)-tagged molecules in live cells to explore the dynamics of protein kinase B (PKB) regulation during B lymphocyte activation. The data show that triggering of the B cell antigen receptor (BCR) induces a transient membrane localization of PKB but a sustained activation of the enzyme; active PKB is found in the cytosol and nuclei of activated B cells. Hence, PKB has three potential sites of action in B lymphocytes; transiently after BCR triggering PKB can phosphorylate plasma membrane localized targets, whereas during the sustained B cell response to antigen, PKB acts in the nucleus and the cytosol. Membrane translocation of PKB and subsequent PKB activation are dependent on BCR activation of phosphatidylinositol 3-kinase (PI3K). Moreover, PI3K signals are both necessary and sufficient for sustained activation of PKB in B lymphocytes. However, under conditions of continuous PI3K activation or BCR triggering there is only transient recruitment of PKB to the plasma membrane, indicating that there must be a molecular mechanism to dissociate PKB from sites of PI3K activity in B cells. The inhibitory Fc receptor, the FcγRIIB, mediates vital homeostatic control of B cell function by recruiting an inositol 5 phosphatase SHIP into the BCR complex. Herein we show that coligation of the BCR with the inhibitory FcγRIIB prevents membrane targeting of PKB. The FcγRIIB can thus antagonize BCR signals for PKB localization and prevent BCR stimulation of PKB activity which demonstrates the mechanism for the inhibitory action of the FcγRIIB on the BCR/PKB response.

scholarly journals CD40 and B cell antigen receptor dual triggering of resting B lymphocytes turns on a partial germinal center phenotype.

1996 ◽  
Vol 183 (1) ◽  
pp. 77-85 ◽  
Author(s):  
L Galibert ◽  
N Burdin ◽  
B de Saint-Vis ◽  
P Garrone ◽  
C Van Kooten ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
Germinal Center ◽  
Culture Conditions ◽  
B Cell Antigen Receptor ◽  
Cd40 Ligation ◽  
Ifn Gamma ◽  
Cell Antigen Receptor ◽  
Cell Antigen

Phenotypic alterations occur when resting human B lymphocytes become germinal center (GC) cells. These include the induction of surface CD38, CD95 (FAS/APO-1), and carboxy-peptidase-M (CPM), a recently described GC marker. However, the factors that govern the in vivo induction of these surface molecules on B cells remain unknown. Here, we purified resting (CD38-) human B lymphocytes from tonsils in an attempt to establish culture conditions resulting in the induction of these three GC markers. We show that interferon (IFN) alpha or IFN-gamma, as well as antibodies against the B cell antigen receptor (BCR), could induce CD38 on resting B lymphocytes, a phenomenon further enhanced by CD40 stimulation. Concomitantly, CD95 was upregulated by CD40 ligation and, to a lesser extent, by IFN-gamma. By contrast, CPM expression could be upregulated only through BCR triggering. This CPM induction was specifically enhanced by CD19 or CD40 ligation. CD40 + BCR stimulation of resting B cells with CD40 ligand-transfected fibroblastic cells in the presence of cross-linked anti-BCR monoclonal antibodies resulted in the coexpression of CD38, CD95, and CPM. As GC cells, these cells also expressed CD71, CD80 (B7.1), and CD86 (B7.2), but not CD24. However, CD10+ or CD44- B cells could not be detected in these culture conditions, suggesting that yet other signals are required for the induction of these GC markers. Consistent with a GC phenotype, CD40 + BCR-stimulated cells exhibited reduced viability when cultured for 20 h in the absence of stimulus. These results first demonstrate that cotriggering of resting B cells through BCR and CD40 induces both phenotypic and functional GC features. They also show that IFN and CD19 triggering of resting B cells specifically modulate the expression of GC markers.

Protein kinase Cβ is critical for the metabolic switch to glycolysis following B-cell antigen receptor engagement

2012 ◽  
Vol 448 (1) ◽  
pp. 165-169 ◽  
Author(s):  
Derek Blair ◽  
Fay J. Dufort ◽  
Thomas C. Chiles
Keyword(s):  
B Cells ◽  
Protein Kinase ◽  
B Cell ◽  
Aerobic Glycolysis ◽  
Antigen Receptor ◽  
Metabolic Reprogramming ◽  
B Cell Antigen Receptor ◽  
Metabolic Switch ◽  
Cell Antigen Receptor ◽  
Cell Antigen

Signals derived from the BCR (B-cell antigen receptor) control survival, development and antigenic responses. One mechanism by which BCR signals may mediate these responses is by regulating cell metabolism. Indeed, the bioenergetic demands of naïve B-cells increase following BCR engagement and are characterized by a metabolic switch to aerobic glycolysis; however, the signalling pathways involved in this metabolic reprogramming are poorly defined. The PKC (protein kinase C) family plays an integral role in B-cell survival and antigenic responses. Using pharmacological inhibition and mice deficient in PKCβ, we demonstrate an essential role of PKCβ in BCR-induced glycolysis in B-cells. In contrast, mice deficient in PKCδ exhibit glycolytic rates comparable with those of wild-type B-cells following BCR cross-linking. The induction of several glycolytic genes following BCR engagement is impaired in PKCβ-deficient B-cells. Moreover, blocking glycolysis results in decreased survival of B-cells despite BCR engagement. The results establish a definitive role for PKCβ in the metabolic switch to glycolysis following BCR engagement of naïve B-cells.

Association of protein kinase C-δ with the B cell antigen receptor complex

2007 ◽  
Vol 19 (4) ◽  
pp. 715-722 ◽  
Author(s):  
Catrin Pracht ◽  
Susana Minguet ◽  
Michael Leitges ◽  
Michael Reth ◽  
Michael Huber
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
B Cell ◽  
Antigen Receptor ◽  
B Cell Antigen Receptor ◽  
Receptor Complex ◽  
Cell Antigen Receptor ◽  
Cell Antigen ◽  
Kinase C

Identification of the SH2 Domain Binding Protein of Bruton’s Tyrosine Kinase as BLNK—Functional Significance of Btk-SH2 Domain in B-Cell Antigen Receptor-Coupled Calcium Signaling

Blood ◽  
1999 ◽  
Vol 94 (7) ◽  
pp. 2357-2364 ◽  
Author(s):  
Shoji Hashimoto ◽  
Akihiro Iwamatsu ◽  
Masamichi Ishiai ◽  
Katsuya Okawa ◽  
Tomoki Yamadori ◽  
...  
Keyword(s):  
B Cells ◽  
Tyrosine Kinase ◽  
Calcium Signaling ◽  
B Cell ◽  
Functional Significance ◽  
Antigen Receptor ◽  
Sh2 Domain ◽  
B Cell Antigen Receptor ◽  
Cell Antigen Receptor ◽  
Cell Antigen

Bruton’s tyrosine kinase (Btk) is a critical component in the B-cell antigen receptor (BCR)-coupled signaling pathway. Its deficiency in B cells leads to loss or marked reduction in the BCR-induced calcium signaling. It is known that this BCR-induced calcium signaling depends on the activation of phospholipase Cγ (PLCγ), which is mediated by Btk and another tyrosine kinase Syk and that the SH2 and pleckstrin homology (PH) domains of Btk play important roles in this activation process. Although the importance of the PH domain of Btk has been explained by its role in the membrane targeting of Btk, the functional significance of the SH2 domain in the calcium signaling has remained merely a matter of speculation. In this report, we identify that one of the major Btk-SH2 domain-binding proteins in B cells is BLNK (B-cell linker protein) and present evidences that the interaction of BLNK and the SH2 domain of Btk contributes to the complete tyrosine phosphorylation of PLCγ.

scholarly journals Unique Signaling Properties of B Cell Antigen Receptor in Mature and Immature B Cells: Implications for Tolerance and Activation

2001 ◽  
Vol 167 (8) ◽  
pp. 4172-4179 ◽  
Author(s):  
Robert J. Benschop ◽  
Erin Brandl ◽  
Andrew C. Chan ◽  
John C. Cambier
Keyword(s):  
B Cells ◽  
B Cell ◽  
Antigen Receptor ◽  
B Cell Antigen Receptor ◽  
Cell Antigen Receptor ◽  
Cell Antigen ◽  
Immature B Cells

scholarly journals Cutting Edge: B Cell Antigen Receptor Signaling Occurs Outside Lipid Rafts in Immature B Cells

2000 ◽  
Vol 165 (11) ◽  
pp. 6020-6023 ◽  
Author(s):  
Tim W. Sproul ◽  
Sunil Malapati ◽  
Julie Kim ◽  
Susan K. Pierce
Keyword(s):  
B Cells ◽  
B Cell ◽  
Lipid Rafts ◽  
Antigen Receptor ◽  
Cutting Edge ◽  
B Cell Antigen Receptor ◽  
Cell Antigen Receptor ◽  
Cell Antigen ◽  
Antigen Receptor Signaling ◽  
Immature B Cells
Sign in / Sign up

Export Citation Format

Share Document