B-cell antigen receptor activates transcription factors NFAT (nuclear factor of activated T-cells) and NF-κB (nuclear factor κB) via a mechanism that involves diacylglycerol

2004 ◽  
Vol 32 (1) ◽  
pp. 113-115 ◽  
Author(s):  
P. Antony ◽  
J.B. Petro ◽  
G. Carlesso ◽  
N.P. Shinners ◽  
J. Lowe ◽  
...  
Keyword(s):  
T Cells ◽  
Transcription Factors ◽  
B Cell ◽  
Antigen Receptor ◽  
Nuclear Factor Κb ◽  
B Cell Antigen Receptor ◽  
Nuclear Factor ◽  
Activated T Cells ◽  
Cell Antigen Receptor ◽  
Cell Antigen

Engagement of the B-cell antigen receptor (BCR) induces the activation of various transcription factors, including NFAT (nuclear factor of activated T-cells) and NF-κB (nuclear factor κB), which participate in long-term biological responses such as proliferation, survival and differentiation of B-lymphocytes. We addressed the biochemical basis of this process using the DT40 chicken B-cell lymphoma. We discovered that Bruton's tyrosine kinase (BTK) and phospholipase C-γ2 (PLC-γ2) are required to activate NFAT and NF-κB, and to produce the lipid second messenger diacylglycerol in response to BCR cross-linking. Therefore the functional integrity of the BTK/PLC-γ2/diacylglycerol signalling axis is crucial for BCR-directed activation of both transcription factors NFAT and NF-κB.

scholarly journals Self-Tolerance Checkpoints in CD4 T Cells Specific for a Peptide Derived from the B Cell Antigen Receptor

2011 ◽  
Vol 187 (1) ◽  
pp. 82-91 ◽  
Author(s):  
Thiago Detanico ◽  
Ryan A. Heiser ◽  
Katja Aviszus ◽  
Cristina Bonorino ◽  
Lawrence J. Wysocki
Keyword(s):  
T Cells ◽  
B Cell ◽  
Cd4 T Cells ◽  
Antigen Receptor ◽  
B Cell Antigen Receptor ◽  
Cell Antigen Receptor ◽  
Cell Antigen ◽  
Self Tolerance

The adaptor protein 3BP2 associates with VAV guanine nucleotide exchange factors to regulate NFAT activation by the B-cell antigen receptor

Blood ◽  
2005 ◽  
Vol 105 (3) ◽  
pp. 1106-1113 ◽  
Author(s):  
Isabelle Foucault ◽  
Séverine Le Bras ◽  
Céline Charvet ◽  
Chéol Moon ◽  
Amnon Altman ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Fate ◽  
Antigen Receptor ◽  
Adaptor Protein ◽  
B Cell Antigen Receptor ◽  
Nucleotide Exchange ◽  
Activated T Cells ◽  
Cell Antigen Receptor ◽  
Cell Antigen ◽  
Bcr Signaling

Abstract Engagement of the B-cell antigen receptor (BCR) activates kinases of the Src and Syk families and signaling complexes assembled by adaptor proteins, which dictate B-cell fate and function. The adaptor 3BP2/SH3BP2, an Abl Src homology domain 3 (SH3)–binding and Syk-kinases interacting protein, exhibits positive regulatory roles in T, natural killer (NK), and basophilic cells. However, its involvement in BCR signaling is completely unknown. Here we show that 3BP2 is tyrosine phosphorylated following BCR aggregation on B lymphoma cells, and that 3BP2 is a substrate for Syk and Fyn, but not Btk. To further explore the function of 3BP2 in B cells, we screened a yeast 2-hybrid B-lymphocyte library and found 3BP2 as a binding partner of Vav proteins. The interaction between 3BP2 and Vav proteins involved both constitutive and inducible mechanisms. 3BP2 also interacted with other components of the BCR signaling pathway, including Syk and phospholipase C γ (PLC-γ). Furthermore, overexpression and RNAi blocking experiments showed that 3BP2 regulated BCR-mediated activation of nuclear factor of activated T cells (NFATs). Finally, evidence was provided that 3BP2 functionally cooperates with Vav proteins and Rho GTPases to activate NFATs. Our results show that 3BP2 may regulate BCR-mediated gene activation through Vav proteins.

scholarly journals B Cell Antigen Receptor Endocytosis and Antigen Presentation to T Cells Require Vav and Dynamin

2009 ◽  
Vol 284 (36) ◽  
pp. 24088-24097 ◽  
Author(s):  
Shikha Malhotra ◽  
Susan Kovats ◽  
Weiguo Zhang ◽  
K. Mark Coggeshall
Keyword(s):  
T Cells ◽  
B Cell ◽  
Antigen Presentation ◽  
Antigen Receptor ◽  
B Cell Antigen Receptor ◽  
Cell Antigen Receptor ◽  
Cell Antigen ◽  
Receptor Endocytosis

scholarly journals The B Lymphocyte Adaptor Molecule of 32 kD (Bam32) Regulates B Cell Antigen Receptor Signaling and Cell Survival

2002 ◽  
Vol 195 (1) ◽  
pp. 143-149 ◽  
Author(s):  
Hiroaki Niiro ◽  
Akito Maeda ◽  
Tomohiro Kurosaki ◽  
Edward A. Clark
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Survival ◽  
Phospholipase C ◽  
B Lymphocyte ◽  
Antigen Receptor ◽  
B Cell Antigen Receptor ◽  
Nuclear Factor ◽  
Cell Antigen Receptor ◽  
Cell Antigen

The B lymphocyte–associated adaptor protein 32 kD in size (Bam32) is expressed at high levels in germinal center (GC) B cells. It has an NH2-terminal src homology 2 (SH2) domain which binds phospholipase C (PLC)γ2, and a COOH-terminal pleckstrin homology (PH) domain. Thus, Bam32 may function to integrate protein tyrosine kinase (PTK) and phosphatidylinositol 3-kinase (PI3K) signaling pathways in B cells. To further define the role Bam32 plays in B cells, we generated Bam32-deficient DT40 cells. These Bam32−/− cells exhibited lower levels of B cell antigen receptor (BCR)-induced calcium mobilization with modest decreases in tyrosine phosphorylation of phospholipase C (PLC)γ2. Moreover, BCR-induced activation of extracellular signal-regulated kinase (ERK), c-jun NH2-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) pathways was impaired in Bam32−/− cells but not the activation of Akt-related pathways. Activation of downstream transcription factors such as nuclear factor of activated T cells (NF-AT) and nuclear factor of κ binding (NF-κB) was also impaired in Bam32−/− cells. Furthermore, Bam32−/− cells were more susceptible to BCR-induced death. Taken together, these findings suggest that Bam32 functions to regulate BCR-induced signaling and cell survival most likely in germinal centers.

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