scholarly journals Inhibition of Fcγ Receptor-Mediated Phagocytosis by a Nonphagocytic Fcγ Receptor

Blood ◽  
1998 ◽  
Vol 91 (5) ◽  
pp. 1762-1768 ◽  
Author(s):  
Sharon Hunter ◽  
Zena K. Indik ◽  
Moo-Kyung Kim ◽  
M. Danielle Cauley ◽  
Jong-Gu Park ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Activation ◽  
Cytoplasmic Domain ◽  
Inhibitory Effect ◽  
B Cell Antigen Receptor ◽  
B Cell Activation ◽  
Fcγ Receptor ◽  
Γ Subunit ◽  
Molecular Events

There are three major classes of human Fcγ receptors (FcγRI, FcγRII, and FcγRIII) and various isoforms of each class are capable of mediating phagocytosis. FcγRIIA is an unusual Fcγ receptor in that it transmits a phagocytic signal in the absence of an additional receptor subunit. The cytoplasmic domain of FcγRIIA contains a conserved motif containing two copies of the sequence YXXL. The tyrosines (Y) within the motif are phosphorylated after receptor crosslinking and the integrity of these conserved sequences is required for efficient phagocytosis. The FcγRIIB receptors, FcγRIIB1 and FcγRIIB2, contain one copy of the cytoplasmic YXXL sequence and do not transmit a phagocytic signal. In B cells, FcγRIIB negatively regulates B-cell activation by the B-cell antigen receptor. Human macrophages express both FcγRIIA and FcγRIIB and while FcγRIIA mediates phagocytosis, the function of FcγRIIB in these cells is unknown. Using the epithelial/fibroblast-like cell line COS-1 as a model to examine the molecular events that regulate the phagocytosis of IgG-coated cells (EA), we investigated the effect of FcγRIIB on FcγRIIA signaling. FcγRIIB inhibited phagocytosis mediated both by FcγRIIA and by a chimeric FcγRIIA receptor containing the extracellular domain of FcγRI and the transmembrane and cytoplasmic domains of FcγRIIA. This inhibition occurred at an early signaling stage because tyrosine phosphorylation of the FcγRIIA cytoplasmic domain was inhibited after concurrent stimulation of these receptors with EA. FcγRIIB mutations showed the importance of the FcγRIIB YXXL for inhibition of FcγRIIA-mediated phagocytosis. Deletion of the FcγRIIB YXXL or conservative replacement of the YXXL tyrosine substantially reduced the inhibitory signal. FcγRIIB had a lesser inhibitory effect on phagocytosis by the Fcγ receptor FcγRIIIA, which requires a γ subunit to mediate a phagocytic signal. These results show that FcγRIIB negatively regulates phagocytic signaling by FcγRIIA and suggests that FcγRIIB plays a role in modulating FcγRIIA function in vivo.

scholarly journals Inhibition of Fcγ Receptor-Mediated Phagocytosis by a Nonphagocytic Fcγ Receptor

Blood ◽  
1998 ◽  
Vol 91 (5) ◽  
pp. 1762-1768 ◽  
Author(s):  
Sharon Hunter ◽  
Zena K. Indik ◽  
Moo-Kyung Kim ◽  
M. Danielle Cauley ◽  
Jong-Gu Park ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Activation ◽  
Cytoplasmic Domain ◽  
Inhibitory Effect ◽  
B Cell Antigen Receptor ◽  
B Cell Activation ◽  
Fcγ Receptor ◽  
Γ Subunit ◽  
Molecular Events

Abstract There are three major classes of human Fcγ receptors (FcγRI, FcγRII, and FcγRIII) and various isoforms of each class are capable of mediating phagocytosis. FcγRIIA is an unusual Fcγ receptor in that it transmits a phagocytic signal in the absence of an additional receptor subunit. The cytoplasmic domain of FcγRIIA contains a conserved motif containing two copies of the sequence YXXL. The tyrosines (Y) within the motif are phosphorylated after receptor crosslinking and the integrity of these conserved sequences is required for efficient phagocytosis. The FcγRIIB receptors, FcγRIIB1 and FcγRIIB2, contain one copy of the cytoplasmic YXXL sequence and do not transmit a phagocytic signal. In B cells, FcγRIIB negatively regulates B-cell activation by the B-cell antigen receptor. Human macrophages express both FcγRIIA and FcγRIIB and while FcγRIIA mediates phagocytosis, the function of FcγRIIB in these cells is unknown. Using the epithelial/fibroblast-like cell line COS-1 as a model to examine the molecular events that regulate the phagocytosis of IgG-coated cells (EA), we investigated the effect of FcγRIIB on FcγRIIA signaling. FcγRIIB inhibited phagocytosis mediated both by FcγRIIA and by a chimeric FcγRIIA receptor containing the extracellular domain of FcγRI and the transmembrane and cytoplasmic domains of FcγRIIA. This inhibition occurred at an early signaling stage because tyrosine phosphorylation of the FcγRIIA cytoplasmic domain was inhibited after concurrent stimulation of these receptors with EA. FcγRIIB mutations showed the importance of the FcγRIIB YXXL for inhibition of FcγRIIA-mediated phagocytosis. Deletion of the FcγRIIB YXXL or conservative replacement of the YXXL tyrosine substantially reduced the inhibitory signal. FcγRIIB had a lesser inhibitory effect on phagocytosis by the Fcγ receptor FcγRIIIA, which requires a γ subunit to mediate a phagocytic signal. These results show that FcγRIIB negatively regulates phagocytic signaling by FcγRIIA and suggests that FcγRIIB plays a role in modulating FcγRIIA function in vivo.

scholarly journals Various Types of Dirofilaria immitis Polyproteins Selectively Induce a Th2-Type Immune Response

2003 ◽  
Vol 71 (7) ◽  
pp. 3802-3811 ◽  
Author(s):  
Hiroyuki Tezuka ◽  
Shinjiro Imai ◽  
Shinya Hidano ◽  
Setsuko Tsukidate ◽  
Koichiro Fujita
Keyword(s):  
B Cell ◽  
Dirofilaria Immitis ◽  
Cell Activation ◽  
Immunoglobulin E ◽  
Interleukin 10 ◽  
Inhibitory Effect ◽  
B Cell Activation ◽  
Ifn Γ

ABSTRACT Dirofilaria immitis polyproteins (DiAgs) are found as 15-kDa monomeric and 30-kDa dimeric forms in exceretory-secretory products of the adult worm. We evaluated the ability of various types of recombinant DiAg (rDiAg; V1 and V2 as monomers and V1V2, V2V1, V1V1, and V2V2 as dimers) to influence Th1/Th2 immune responses. V1-, V1Vx- and V2-, V2Vx-driven nonspecific immunoglobulin E (IgE) production peaked at 21 and 14 days after administration, respectively. Dimer-induced IgE response was an interesting biphasic pattern with the second peaks on days 35 (V2Vx) or 42 (V1Vx). Absolute amounts of nonspecific IgE production induced with monomers were larger than those observed with dimers at the first peak. The magnitude of cell expansion and interleukin-10 (IL-10) production in mesenteric lymph node (MLN) B-cell induced with rDiAgs was linked to the levels of the first IgE peak in vivo and IgE produced by rDiAg plus IL-4-stimulated B cells in vitro. All rDiAgs failed to augment IgG2c production. V2 and V2Vx elicited IL-4 production by MLN cells more rapidly than V1 and V1Vx. The inhibitory effect of rDiAg on gamma interferon (IFN-γ) production was stronger in monomers than in dimers. Neutralization of IL-10 restored IFN-γ production, whereas the expression of IL-4 and IgE was partly prevented by depletion of IL-10. These results indicate that monomer rather than dimer is an efficient form of DiAg and suggest that the difference of IgE-inducing capacity among these DiAgs is closely associated with the pattern of both B-cell activation and IL-4 production.

Microsignalosomes: spatially resolved receptor signalling

2009 ◽  
Vol 37 (5) ◽  
pp. 1014-1018 ◽  
Author(s):  
Bebhinn Treanor ◽  
Naomi E. Harwood ◽  
Facundo D. Batista
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Activation ◽  
Imaging Techniques ◽  
Adaptive Immune System ◽  
Cell Receptor ◽  
The Body ◽  
B Cell Activation ◽  
Molecular Events

B-cells are a critical component of the adaptive immune system. As such, B-cells survey the body and mount appropriate protective responses to pathogen-derived antigens, resulting in the production of specific antibodies and induction of immunological memory. Given the effectiveness of these responses in selectively eliminating pathogenic infections, it is clear that the processes underlying antigen-induced B-cell activation must be highly regulated. Somewhat surprisingly given the specialized function of these immune cells, the BCR (B-cell receptor) functions similarly to receptors of the tyrosine kinase family that are commonplace in biology, as BCR ligation with antigen leads to B-cell proliferation and differentiation. In the Lymphocyte Interaction Laboratory, we are particularly interested in characterizing the very early molecular events underlying B-cell activation using a combination of cutting-edge high-resolution and in vivo imaging techniques.

scholarly journals APRIL-Deficient Mice Have Normal Immune System Development

2004 ◽  
Vol 24 (3) ◽  
pp. 997-1006 ◽  
Author(s):  
Eugene Varfolomeev ◽  
Frank Kischkel ◽  
Flavius Martin ◽  
Dhaya Seshasayee ◽  
Hua Wang ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Activation ◽  
System Development ◽  
Physiological Role ◽  
B Cell Activation ◽  
Tnf Superfamily ◽  
Immune System Development ◽  
Humoral Responses

ABSTRACT APRIL (a proliferation-inducing ligand) is a member of the tumor necrosis factor (TNF) superfamily. APRIL mRNA shows high levels of expression in tumors of different origin and a low level of expression in normal cells. APRIL shares two TNF receptor family members, TACI and BCMA, with another TNF homolog, BLyS/BAFF. BLyS is involved in regulation of B-cell activation and survival and also binds to a third receptor, BR3/BAFF-R, which is not shared with APRIL. Recombinant APRIL and BLyS induce accumulation of B cells in mice, while BLyS deficiency results in severe B-cell dysfunction. To investigate the physiological role of APRIL, we generated mice that are deficient in its encoding gene. APRIL−/− mice were viable and fertile and lacked any gross abnormality. Detailed histological analysis did not reveal any defects in major tissues and organs, including the primary and secondary immune organs. T- and B-cell development and in vitro function were normal as well, as were T-cell-dependent and -independent in vivo humoral responses to antigenic challenge. These data indicate that APRIL is dispensable in the mouse for proper development. Thus, BLyS may be capable of fulfilling APRIL's main functions.

scholarly journals Deposition of idiotype-anti-idiotype immune complexes in renal glomeruli after polyclonal B cell activation.

1982 ◽  
Vol 155 (5) ◽  
pp. 1385-1399 ◽  
Author(s):  
M Goldman ◽  
L M Rose ◽  
A Hochmann ◽  
P H Lambert
Keyword(s):  
B Cell ◽  
Immune Complexes ◽  
Cell Activation ◽  
Fluorescein Isothiocyanate ◽  
B Cell Activation ◽  
Cell Repertoire ◽  
Myeloma Protein ◽  
B Cell Repertoire ◽  
Glomerular Lesions

We investigated the possible role of idiotypic interactions in the pathogenesis of the glomerular lesions observed in mice undergoing polyclonal B cell activation. BALB/c mice were studied for the presence of renal deposits of T15 idiotype-anti-T15 idiotype-immune complexes (IC) after injection of bacterial lipopolysaccharides (LPS). The T15 idiotype is the major idiotype of BALB/c mice anti-phosphorylcholine (PC) antibodies, which are cross-reactive with the idiotype of the TEPC-15 myeloma protein. This model was used because T15 idiotype-anti-T15 idiotype IC have been detected in the circulation of BALB/c mice after polyclonal B cell activation. First, an idiotype-specific immunofluorescence technique allowed us to detect T15 idiotype-bearing immunoglobulins in glomeruli from day 6 to day 28 after LPS injection. Second, fluorescein isothiocyanate-conjugated TEPC-15 myeloma protein was found to localize in the glomeruli after in vivo injection 18 d after LPS administration. This renal localization was shown to be idiotype-specific and could be quantified in a trace-labeling experiment. Third, kidney-deposited immunoglobulins of mice injected with LPS were eluted, radiolabeled, and analyzed by radioimmunoassay. Both T15 idiotype-bearing immunoglobulins and anti-T15 idiotype antibodies were detected in the eluates, providing further evidence for a renal deposition of T15 idiotype-anti-T15 idiotype IC. Polyclonal B cell activation is likely to result in a simultaneous triggering of many idiotypic clones and of corresponding anti-idiotypic clones represented in the B cell repertoire. This could lead to the formation of a variety of idiotype-anti-idiotype IC that could participate in the development of glomerular lesions.

scholarly journals Telomerase Activity Is Induced in Human Peripheral B Lymphocytes by the Stimulation to Antigen Receptor

Blood ◽  
1997 ◽  
Vol 89 (4) ◽  
pp. 1299-1307 ◽  
Author(s):  
Hideya Igarashi ◽  
Nobuo Sakaguchi
Keyword(s):  
B Cells ◽  
B Cell ◽  
Peripheral Blood ◽  
Cell Activation ◽  
Interleukin 2 ◽  
Antigen Receptor ◽  
Telomerase Activity ◽  
B Cell Activation ◽  
Molecular Events

Abstract To understand the molecular events for the proliferation of B cells, we studied the induction of telomerase activity in vitro after stimulation to B-cell antigen receptor (BCR) on human peripheral B cells. Although unstimulated purified B cells of tonsils and peripheral blood from healthy volunteers do not express detectable telomerase activity, anti-IgM beads induce telomerase activity in these B cells. Soluble anti-IgM antibody (Ab) alone does not induce telomerase activity, but the second signal, given by either one of the cytokines of interleukin-2 (IL-2), IL-4, and IL-13 or by anti-CD40 monoclonal Ab (MoAb), is effective as the costimulation for the induction of the activity. Stimulation with antiIgM Ab and anti-CD40 MoAb induces telomerase activity in most mature B cells of the tonsils and peripheral blood. The stimuli to both IgM and IgD receptors similarly induce the activity. Induction of telomerase activity is accompanied with the proliferation of B cells, but is not absolutely correlated with the extent of B-cell growth. Phorbol dibutylate (PDB) plus calcium (Ca) ionophore (PDB/Ca), which replace the activation through BCR and the costimulatory molecules, also induce telomerase activity. Moreover, it is suggested that phosphoinositide (PI) 3-kinase plays a role for the induction of telomerase activity in B cells stimulated with anti-IgM Ab and anti-CD40 MoAb. These results suggest that telomerase activity is induced in the B-cell activation of the antigen specific immune response.

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