scholarly journals Distribution of the Src-homology-2-domain-containing inositol 5-phosphatase SHIP-2 in both non-haemopoietic and haemopoietic cells and possible involvement of SHIP-2 in negative signalling of B-cells

1999 ◽  
Vol 342 (3) ◽  
pp. 697-705 ◽  
Author(s):  
Eric MURAILLE ◽  
Xavier PESESSE ◽  
Céline KUNTZ ◽  
Christophe ERNEUX
Keyword(s):  
B Cell ◽  
Cell Activation ◽  
Cell Receptor ◽  
Sh2 Domain ◽  
B Cell Activation ◽  
Mouse Tissues ◽  
Inhibitory Feedback ◽  
Src Homology ◽  
Src Homology 2 Domain ◽  
Haemopoietic Cells

The termination of activation signals is a critical step in the control of the immune response; perturbation of inhibitory feedback pathways results in profound immune defects culminating in autoimmunity and overwhelming inflammation. FcγRIIB receptor is a well described inhibitory receptor. The ligation of B-cell receptor (BCR) and FcγRIIB leads to the inhibition of B-cell activation. Numerous studies have demonstrated that the SH2-domain-containing inositol 5-phosphatase SHIP (referred hereto as SHIP-1) is essential in this process. The cDNA encoding a second SH2-domain-containing inositol 5-phosphatase, SHIP-2, has been cloned [Pesesse, Deleu, De Smedt, Drayer and Erneux (1997) Biochem. Biophys. Res. Commun. 239, 697-700]. Here we report the distribution of SHIP-2 in mouse tissues: a Western blot analysis of mouse tissues reveals that SHIP-2 is expressed in both haemopoietic and non-haemopoietic cells. In addition to T-cell and B-cell lines, spleen, thymus and lung are shown to coexpress SHIP-1 and SHIP-2. Moreover, SHIP-2 is detected in fibroblasts, heart and different brain areas. SHIP-2 shows a maximal tyrosine phosphorylation and association to Shc after ligation of BCR to FcγRIIB but not after stimulation of BCR alone. Our results therefore suggest a possible role for SHIP-2 in the negative regulation of immunocompetent cells.

scholarly journals Actin Depolymerization Transduces the Strength of B-Cell Receptor Stimulation

2005 ◽  
Vol 16 (5) ◽  
pp. 2275-2284 ◽  
Author(s):  
Shengli Hao ◽  
Avery August
Keyword(s):  
B Cell ◽  
Lipid Raft ◽  
Cell Activation ◽  
Cell Receptor ◽  
Dependent Manner ◽  
B Cell Activation ◽  
Erk Activation ◽  
Actin Depolymerization ◽  
Transcription Factor Activation ◽  
Raft Clustering

Polymerization of the actin cytoskeleton has been found to be essential for B-cell activation. We show here, however, that stimulation of BCR induces a rapid global actin depolymerization in a BCR signal strength-dependent manner, followed by polarized actin repolymerization. Depolymerization of actin enhances and blocking actin depolymerization inhibits BCR signaling, leading to altered BCR and lipid raft clustering, ERK activation, and transcription factor activation. Furthermore actin depolymerization by itself induces altered lipid raft clustering and ERK activation, suggesting that F-actin may play a role in separating lipid rafts and in setting the threshold for cellular activation.

scholarly journals Functional Outcome of B Cell Activation by Chromatin Immune Complex Engagement of the B Cell Receptor and TLR9

2007 ◽  
Vol 179 (11) ◽  
pp. 7397-7405 ◽  
Author(s):  
Liliana Busconi ◽  
Jason W. Bauer ◽  
Joseph R. Tumang ◽  
Amy Laws ◽  
Kristin Perkins-Mesires ◽  
...  
Keyword(s):  
B Cell ◽  
Functional Outcome ◽  
Immune Complex ◽  
Cell Activation ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
B Cell Activation

scholarly journals Costimulatory blockade of CD154-CD40 in combination with T-cell lymphodepletion results in prevention of allogeneic sensitization

Blood ◽  
2008 ◽  
Vol 111 (6) ◽  
pp. 3266-3275 ◽  
Author(s):  
Hong Xu ◽  
Jun Yan ◽  
Yiming Huang ◽  
Paula M. Chilton ◽  
Chuanlin Ding ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cell Activation ◽  
Dominant Role ◽  
Combined Treatment ◽  
Cell Receptor ◽  
B Cell Activation ◽  
B Cell Tolerance ◽  
Costimulatory Blockade ◽  
Bone Marrow Engraftment

Abstract Sensitization is a critical unresolved challenge in transplantation. We show for the first time that blockade of CD154 alone or combined with T-cell depletion prevents sensitization. Allogeneic skin grafts were rejected by recipients treated with anti-αβ T-cell receptor (TCR), anti-CD154, anti-OX40L, or anti–inducible costimulatory pathway (ICOS) mAb alone with a kinetic similar to untreated recipients. However, the production of anti–donor MHC antibody was prevented in mice treated with anti-CD154 mAb only, suggesting a specific role for the CD154-CD40 pathway in B-cell activation. The impairment of T cell–dependent B-cell responses by blocking CD154 occurs through inhibiting activation of T and B cells and secretion of IFN-γ and IL-10. Combined treatment with both anti-CD154 and anti–αβ TCR abrogated antidonor antibody production and resulted in prolonged skin graft survival, suggesting the induction of both T- and B-cell tolerance with prevention of allogeneic sensitization. In addition, we show that the tolerance induced by combined treatment was nondeletional. Moreover, these sensitization-preventive strategies promote bone marrow engraftment in recipients previously exposed to donor alloantigen. These findings may be clinically relevant to prevent allosensitization with minimal toxicity and point to humoral immunity as playing a dominant role in alloreactivity in sensitized recipients.

scholarly journals PTIP chromatin regulator controls development and activation of B cell subsets to license humoral immunity in mice

2017 ◽  
Vol 114 (44) ◽  
pp. E9328-E9337 ◽  
Author(s):  
Dan Su ◽  
Stijn Vanhee ◽  
Rebeca Soria ◽  
Elin Jaensson Gyllenbäck ◽  
Linda M. Starnes ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Humoral Immunity ◽  
Cell Activation ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Transactivation Domain ◽  
B Cell Activation ◽  
Chromatin Regulator ◽  
B Cell Subsets

B cell receptor signaling and downstream NF-κB activity are crucial for the maturation and functionality of all major B cell subsets, yet the molecular players in these signaling events are not fully understood. Here we use several genetically modified mouse models to demonstrate that expression of the multifunctional BRCT (BRCA1 C-terminal) domain-containing PTIP (Pax transactivation domain-interacting protein) chromatin regulator is controlled by B cell activation and potentiates steady-state and postimmune antibody production in vivo. By examining the effects of PTIP deficiency in mice at various ages during ontogeny, we demonstrate that PTIP promotes bone marrow B cell development as well as the neonatal establishment and subsequent long-term maintenance of self-reactive B-1 B cells. Furthermore, we find that PTIP is required for B cell receptor- and T:B interaction-induced proliferation, differentiation of follicular B cells during germinal center formation, and normal signaling through the classical NF-κB pathway. Together with the previously identified role for PTIP in promoting sterile transcription at the Igh locus, the present results establish PTIP as a licensing factor for humoral immunity that acts at several junctures of B lineage maturation and effector cell differentiation by controlling B cell activation.

scholarly journals Monovalent engagement of the BCR activates ovalbumin-specific transnuclear B cells

2014 ◽  
Vol 211 (2) ◽  
pp. 365-379 ◽  
Author(s):  
Ana M. Avalos ◽  
Angelina M. Bilate ◽  
Martin D. Witte ◽  
Albert K. Tai ◽  
Jiang He ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Synthetic Peptides ◽  
Cell Activation ◽  
Cell Receptor ◽  
Fine Tuning ◽  
B Cell Activation ◽  
Cd40 Ligation ◽  
Peptide Antigen ◽  
Peptide Epitope

Valency requirements for B cell activation upon antigen encounter are poorly understood. OB1 transnuclear B cells express an IgG1 B cell receptor (BCR) specific for ovalbumin (OVA), the epitope of which can be mimicked using short synthetic peptides to allow antigen-specific engagement of the BCR. By altering length and valency of epitope-bearing synthetic peptides, we examined the properties of ligands required for optimal OB1 B cell activation. Monovalent engagement of the BCR with an epitope-bearing 17-mer synthetic peptide readily activated OB1 B cells. Dimers of the minimal peptide epitope oriented in an N to N configuration were more stimulatory than their C to C counterparts. Although shorter length correlated with less activation, a monomeric 8-mer peptide epitope behaved as a weak agonist that blocked responses to cell-bound peptide antigen, a blockade which could not be reversed by CD40 ligation. The 8-mer not only delivered a suboptimal signal, which blocked subsequent responses to OVA, anti-IgG, and anti-kappa, but also competed for binding with OVA. Our results show that fine-tuning of BCR-ligand recognition can lead to B cell nonresponsiveness, activation, or inhibition.

Enhanced B Cell Activation in the Absence of CD81

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2578-2578
Author(s):  
Mrinmoy Sanyal ◽  
Rosemary Fernandez ◽  
Shoshana Levy
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Activation ◽  
Cell Receptor ◽  
Free Calcium ◽  
B Cell Activation ◽  
Membrane Reorganization ◽  
A Cell

Abstract CD81 is a component of the CD19/CD21 coreceptor complex in B cells. This tetraspanin molecule was previously shown to enable membrane reorganization in B cells responding to complement-bound antigens. Here we stimulated B cells via their B cell receptor (BCR) and demonstrate that Cd81−/− B cells fluxed higher intracellular free calcium ion along with increased phosphorylation of PLCγ2 and Syk. The stimulated Cd81−/− B cells also proliferated faster and secreted higher amounts of antibodies. Moreover, activation of the TLR4 pathway in Cd81−/− B cells induced increased proliferation and antibody secretion. Furthermore, Cd81−/− mice mounted a significantly higher immune response to T-cell independent antigens than their wildtype counterparts. Finally, analysis of Cd81−/− B cells that were generated by bone marrow transplantation into Rag1−/− mice confirmed a cell intrinsic hyperactive phenotype. Taken together, these results indicate that CD81 plays a negative role in B cell activation in vitro and in vivo.

CD19 is essential for B cell activation by promoting B cell receptor–antigen microcluster formation in response to membrane-bound ligand

2007 ◽  
Vol 9 (1) ◽  
pp. 63-72 ◽  
Author(s):  
David Depoil ◽  
Sebastian Fleire ◽  
Bebhinn L Treanor ◽  
Michele Weber ◽  
Naomi E Harwood ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Activation ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
B Cell Activation ◽  
Membrane Bound

scholarly journals Utilization of a photoactivatable antigen system to examine B-cell probing termination and the B-cell receptor sorting mechanisms during B-cell activation

2016 ◽  
Vol 113 (5) ◽  
pp. E558-E567 ◽  
Author(s):  
Jing Wang ◽  
Shan Tang ◽  
Zhengpeng Wan ◽  
Yiren Gao ◽  
Yiyun Cao ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Single Molecule ◽  
Cell Activation ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Antigen Binding ◽  
B Cell Activation ◽  
Class I Mhc ◽  
Antigen System

Antigen binding to the B-cell receptor (BCR) induces several responses, resulting in B-cell activation, proliferation, and differentiation. However, it has been difficult to study these responses due to their dynamic, fast, and transient nature. Here, we attempted to solve this problem by developing a controllable trigger point for BCR and antigen recognition through the construction of a photoactivatable antigen, caged 4-hydroxy-3-nitrophenyl acetyl (caged-NP). This photoactivatable antigen system in combination with live cell and single molecule imaging techniques enabled us to illuminate the previously unidentified B-cell probing termination behaviors and the precise BCR sorting mechanisms during B-cell activation. B cells in contact with caged-NP exhibited probing behaviors as defined by the unceasing extension of membrane pseudopods in random directions. Further analyses showed that such probing behaviors are cell intrinsic with strict dependence on F-actin remodeling but not on tonic BCR signaling. B-cell probing behaviors were terminated within 4 s after photoactivation, suggesting that this response was sensitive and specific to BCR engagement. The termination of B-cell probing was concomitant with the accumulation response of the BCRs into the BCR microclusters. We also determined the Brownian diffusion coefficient of BCRs from the same B cells before and after BCR engagement. The analysis of temporally segregated single molecule images of both BCR and major histocompatibility complex class I (MHC-I) demonstrated that antigen binding induced trapping of BCRs into the BCR microclusters is a fundamental mechanism for B cells to acquire antigens.

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