scholarly journals Rapid elimination of mature autoreactive B cells demonstrated by Cre-induced change in B cell antigen receptor specificity in vivo

1998 ◽  
Vol 95 (22) ◽  
pp. 13171-13175 ◽  
Author(s):  
K.-P. Lam ◽  
K. Rajewsky
Keyword(s):  
B Cells ◽  
B Cell ◽  
Antigen Receptor ◽  
B Cell Antigen Receptor ◽  
Receptor Specificity ◽  
Autoreactive B Cells ◽  
Cell Antigen Receptor ◽  
Cell Antigen ◽  
Rapid Elimination

scholarly journals RNA-associated autoantigens activate B cells by combined B cell antigen receptor/Toll-like receptor 7 engagement

2005 ◽  
Vol 202 (9) ◽  
pp. 1171-1177 ◽  
Author(s):  
Christina M. Lau ◽  
Courtney Broughton ◽  
Abigail S. Tabor ◽  
Shizuo Akira ◽  
Richard A. Flavell ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Antigen Receptor ◽  
Adaptor Protein ◽  
B Cell Antigen Receptor ◽  
Toll Like Receptor ◽  
Autoreactive B Cells ◽  
Cell Antigen Receptor ◽  
Cell Antigen

Previous studies (Leadbetter, E.A., I.R. Rifkin, A.H. Hohlbaum, B. Beaudette, M.J. Shlomchik, and A. Marshak-Rothstein. 2002. Nature. 416:603–607; Viglianti, G.A., C.M. Lau, T.M. Hanley, B.A. Miko, M.J. Shlomchik, and A. Marshak-Rothstein. 2003. Immunity. 19:837–847) established the unique capacity of DNA and DNA-associated autoantigens to activate autoreactive B cells via sequential engagement of the B cell antigen receptor (BCR) and Toll-like receptor (TLR) 9. We demonstrate that this two-receptor paradigm can be extended to the BCR/TLR7 activation of autoreactive B cells by RNA and RNA-associated autoantigens. These data implicate TLR recognition of endogenous ligands in the response to both DNA- and RNA-associated autoantigens. Importantly, the response to RNA-associated autoantigens was markedly enhanced by IFN-α, a cytokine strongly linked to disease progression in patients with systemic lupus erythematosus (SLE). As further evidence that TLRs play a key role in autoantibody responses in SLE, we found that autoimmune-prone mice, lacking the TLR adaptor protein MyD88, had markedly reduced chromatin, Sm, and rheumatoid factor autoantibody titers.

scholarly journals A VH11Vκ9 B Cell Antigen Receptor Drives Generation of CD5+ B Cells Both In Vivo and In Vitro

2000 ◽  
Vol 164 (9) ◽  
pp. 4586-4593 ◽  
Author(s):  
Michael J. Chumley ◽  
Joseph M. Dal Porto ◽  
Susumu Kawaguchi ◽  
John C. Cambier ◽  
David Nemazee ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Antigen Receptor ◽  
B Cell Antigen Receptor ◽  
Cell Antigen Receptor ◽  
Cell Antigen

scholarly journals Expansion or Elimination of B Cells In Vivo: Dual Roles for CD40- and Fas (CD95)-Ligands Modulated by the B Cell Antigen Receptor

Cell ◽  
1996 ◽  
Vol 87 (2) ◽  
pp. 319-329 ◽  
Author(s):  
Jeffrey C Rathmell ◽  
Sarah E Townsend ◽  
Jiachao C Xu ◽  
Richard A Flavell ◽  
Christopher C Goodnow
Keyword(s):  
B Cells ◽  
B Cell ◽  
Antigen Receptor ◽  
B Cell Antigen Receptor ◽  
Dual Roles ◽  
Cell Antigen Receptor ◽  
Cell Antigen

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 Grb2 and GRAP connect the B cell antigen receptor to Erk MAP kinase activation in human B cells

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Kanika Vanshylla ◽  
Caren Bartsch ◽  
Christoffer Hitzing ◽  
Laura Krümpelmann ◽  
Jürgen Wienands ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Map Kinase ◽  
Antigen Receptor ◽  
B Cell Antigen Receptor ◽  
Kinase Activation ◽  
Cell Antigen Receptor ◽  
Cell Antigen ◽  
Human B Cells

scholarly journals Cbl-b Negatively Regulates B Cell Antigen Receptor Signaling in Mature B Cells through Ubiquitination of the Tyrosine Kinase Syk

2003 ◽  
Vol 197 (11) ◽  
pp. 1511-1524 ◽  
Author(s):  
Hae Won Sohn ◽  
Hua Gu ◽  
Susan K. Pierce
Keyword(s):  
B Cells ◽  
Tyrosine Kinase ◽  
B Cell ◽  
Antigen Receptor ◽  
Cellular Systems ◽  
Cross Linking ◽  
B Cell Antigen Receptor ◽  
Cell Antigen Receptor ◽  
Cell Antigen ◽  
Bcr Signaling

Members of the Cbl family of molecular adaptors play key roles in regulating tyrosine kinase-dependent signaling in a variety of cellular systems. Here we provide evidence that in B cells Cbl-b functions as a negative regulator of B cell antigen receptor (BCR) signaling during the normal course of a response. In B cells from Cbl-b–deficient mice cross-linking the BCRs resulted in sustained phosphorylation of Igα, Syk, and phospholipase C (PLC)-γ2, leading to prolonged Ca2+ mobilization, and increases in extracellular signal–regulated kinase (ERK) and c-Jun NH2-terminal protein kinase (JNK) phosphorylation and surface expression of the activation marker, CD69. Image analysis following BCR cross-linking showed sustained polarization of the BCRs into large signaling-active caps associated with phosphorylated Syk in Cbl-b–deficient B cells in contrast to the BCRs in Cbl-b–expressing B cells that rapidly proceeded to form small, condensed, signaling inactive caps. Significantly, prolonged phosphorylation of Syk correlated with reduced ubiquitination of Syk indicating that Cbl-b negatively regulates BCR signaling by targeting Syk for ubiquitination.

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