The B cell antigen receptor in B-cell development

1994 ◽  
Vol 6 (2) ◽  
pp. 248-256 ◽  
Author(s):  
Stephen Desiderio
Keyword(s):  
B Cell ◽  
Antigen Receptor ◽  
Cell Development ◽  
B Cell Development ◽  
B Cell Antigen Receptor ◽  
Cell Antigen Receptor ◽  
Cell Antigen

scholarly journals Kidins220/ARMS binds to the B cell antigen receptor and regulates B cell development and activation

2015 ◽  
Vol 212 (10) ◽  
pp. 1693-1708 ◽  
Author(s):  
Gina J. Fiala ◽  
Iga Janowska ◽  
Fabiola Prutek ◽  
Elias Hobeika ◽  
Annyesha Satapathy ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Activation ◽  
Antigen Receptor ◽  
Cell Development ◽  
B Cell Development ◽  
B Cell Antigen Receptor ◽  
Independent Manner ◽  
Cell Antigen Receptor ◽  
Cell Antigen ◽  
Bcr Signaling

B cell antigen receptor (BCR) signaling is critical for B cell development and activation. Using mass spectrometry, we identified a protein kinase D–interacting substrate of 220 kD (Kidins220)/ankyrin repeat–rich membrane-spanning protein (ARMS) as a novel interaction partner of resting and stimulated BCR. Upon BCR stimulation, the interaction increases in a Src kinase–independent manner. By knocking down Kidins220 in a B cell line and generating a conditional B cell–specific Kidins220 knockout (B-KO) mouse strain, we show that Kidins220 couples the BCR to PLCγ2, Ca2+, and extracellular signal-regulated kinase (Erk) signaling. Consequently, BCR-mediated B cell activation was reduced in vitro and in vivo upon Kidins220 deletion. Furthermore, B cell development was impaired at stages where pre-BCR or BCR signaling is required. Most strikingly, λ light chain–positive B cells were reduced sixfold in the B-KO mice, genetically placing Kidins220 in the PLCγ2 pathway. Thus, our data indicate that Kidins220 positively regulates pre-BCR and BCR functioning.

scholarly journals The Immunoglobulin (Ig)α and Igβ Cytoplasmic Domains Are Independently Sufficient to Signal B Cell Maturation and Activation in Transgenic Mice

1997 ◽  
Vol 185 (10) ◽  
pp. 1753-1758 ◽  
Author(s):  
Yih-Miin Teh ◽  
Michael S. Neuberger
Keyword(s):  
B Cell ◽  
Transgenic Mouse ◽  
Critical Role ◽  
Antigen Receptor ◽  
Cell Development ◽  
B Cell Development ◽  
Allelic Exclusion ◽  
B Cell Antigen Receptor ◽  
Cell Antigen Receptor ◽  
Cell Antigen

The B cell antigen receptor, composed of membrane immunoglobulin (Ig) sheathed by the Igα/Igβ heterodimer plays a critical role in mediating B cell development and responses to antigen. The cytoplasmic tails of Igα and Igβ differ substantially but have been well conserved in evolution. Transfection experiments have revealed that, while these tails share an esssential tyrosine-based activation motif (ITAM), they perform differently in some but not all assays and have been proposed to recruit distinct downstream effectors. We have created transgenic mouse lines expressing chimeric receptors comprising an IgM fused to the cytoplasmic domain of each of the sheath polypeptides. IgM/α and IgM/β chimeras (but not an IgM/β with mutant ITAM) are each independently sufficient to mediate allelic exclusion, rescue B cell development in gene-targeted Igμ− mice that lack endogenous antigen receptors, as well as signal for B7 upregulation. While the (IgM/α) × (IgM/β) double-transgenic mouse revealed somewhat more efficient allelic exclusion, our data indicate that each of the sheath polypeptides is sufficient to mediate many of the essential functions of the B cell antigen receptor, even if the combination gives optimal activity.

scholarly journals The B Cell Antigen Receptor Controls Integrin Activity through Btk and PLCγ2

2003 ◽  
Vol 198 (10) ◽  
pp. 1539-1550 ◽  
Author(s):  
Marcel Spaargaren ◽  
Esther A. Beuling ◽  
Mette L. Rurup ◽  
Helen P. Meijer ◽  
Melanie D. Klok ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
B Cell ◽  
Critical Role ◽  
Antigen Receptor ◽  
Cell Development ◽  
B Cell Development ◽  
Mitogen Activated Protein Kinase ◽  
B Cell Antigen Receptor ◽  
Cell Antigen Receptor ◽  
Cell Antigen

Integrin-mediated adhesion and B cell antigen receptor (BCR) signaling play a critical role in B cell development and function, including antigen-specific B cell differentiation. Here we show that the BCR controls integrin α4β1 (VLA-4)-mediated adhesion of B cells to vascular cell adhesion molecule-1 and fibronectin. Molecular dissection of the underlying signaling mechanism by a combined biochemical, pharmacological, and genetic approach demonstrates that this BCR-controlled integrin-mediated adhesion requires the (consecutive) activation of Lyn, Syk, phosphatidylinositol 3-kinase, Bruton's tyrosine kinase (Btk), phospholipase C (PLC)γ2, IP3R-mediated Ca2+ release, and PKC. In contrast, activation of mitogen-activated protein kinase kinase (MEK) or extracellular signal–regulated kinase (ERK) is not required, and simultaneous activation of MEK, ERK, and PKB is not sufficient either. Furthermore, Btk is also involved in the control of integrin-mediated adhesion of preB cells. The control of integrin α4β1-mediated B cell adhesion by the BCR involves cytoskeletal reorganization and integrin clustering. These results reveal a novel function for the BCR and Btk, i.e., regulation of integrin α4β1 activity, thereby providing new insights into the control of B cell development and differentiation, as well as into the pathogenesis of the immunodeficiency disease X-linked agammaglobulineamia (XLA).

B cell antigen receptor cross-linking induces tyrosine phosphorylation and membrane translocation of a multimeric Shc complex that is augmented by CD19 co-ligation

1994 ◽  
Vol 24 (11) ◽  
pp. 2818-2825 ◽  
Author(s):  
Arjan C. Lankester ◽  
Gijs M. W. Van Schijndel ◽  
Pauline M. L. Rood ◽  
Arthur J. Verhoeven ◽  
René A. W. Van Lier
Keyword(s):  
B Cell ◽  
Tyrosine Phosphorylation ◽  
Antigen Receptor ◽  
Cross Linking ◽  
B Cell Antigen Receptor ◽  
Membrane Translocation ◽  
Cell Antigen Receptor ◽  
Cell Antigen
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