Inducible Expression of the gp49B Inhibitory Receptor on NK Cells

Wang, Lawrence L.; Chu, Dortha T.; Dokun, Ayotunde O.; Yokoyama, Wayne M.

doi:10.4049/jimmunol.164.10.5215

Cited by 64 publications

(51 citation statements)

References 35 publications

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“…These considerations demonstrate the necessity of additional experimental work following initial microarray-based screening for relevant genes. Our finding of an antiproliferative and also toxic effect of GP49B was in good agreement with previous work, showing the inhibitory action of this Ig superfamily- (Wang et al, 2000). Our results suggest the existence of a receptor-mediated inhibitory pathway in pro B-cells that counteracts the IL-3 mitogenic signal.…”

Section: Discussionsupporting

confidence: 82%

“…Only paclitaxel did not cause an induction of known p53 target genes. An inhibitory function had also been described previously for the glycoprotein GP49B (Wang et al, 2000) that we identified as induced in the camptothecin, cisplatin and paclitaxel responses. Induction of a murine homologue of the inhibitory protein tob (Matsuda et al, 1996) was observed in the camptothecin, cisplatin and methotrexate responses, further confirming the hypothesis that pathway intersections of upregulated transcripts should be enriched for anti-proliferative genes.…”

Section: Gene Expression Analysis By Cdna Microarraysmentioning

confidence: 99%

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A microarray-based, integrated approach to identify novel regulators of cancer drug response and apoptosis

et al. 2002

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Section: Discussionsupporting

confidence: 82%

Section: Gene Expression Analysis By Cdna Microarraysmentioning

confidence: 99%

A microarray-based, integrated approach to identify novel regulators of cancer drug response and apoptosis

et al. 2002

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“…We examined the surface expression of gp49A and gp49B on BMDC and splenic CD11c 1 DC either from B6 or gp49B À/À mice as well as on the BMDC after stimulation with LPS or addition of OVA by flow cytometry with mAb H1.1, which recognizes a common epitope on gp49A and gp49B [35]. As shown in Fig.…”

Section: Bmdc and Splenic DC Express Gp49bmentioning

confidence: 99%

“…Colligation of gp49B with the highaffinity receptor for IgE or the type I FcgR by antibodies inhibits degranulation of mast cells or production of TNF-a by macrophages, respectively [29,34]. Recently, it was reported that gp49B expression can be induced on activated T cells and NK cells stimulated by IL-2, or viral or bacterial infection, and that it regulates IFN-g production and NK cell-mediated cell lysis [35,36]. In in vivo studies, gp49B-deficient (gp49B À/À ) mice exhibited increased severity of passive and active cutaneous anaphylaxis [26].…”

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confidence: 99%

A novel regulatory role of gp49B on dendritic cells in T‐cell priming

et al. 2008

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Dendritic cells (DC) play pivotal roles in the induction and regulation of both innate and acquired immunity. DC express several cell-surface immune inhibitory receptors. However, little is known about their potential immunoregulatory functions in the context of T-cell activation. Here we report that murine gp49B, a member of the immunoglobulin superfamily, harboring immunoreceptor tyrosine-based inhibitory motifs, is expressed on DC and downregulates cellular activity to prevent the excessive activation of T cells in vitro and in vivo. Bone marrow-derived DC (BMDC) from newly generated gp49B-deficient (gp49B À/À ) mice induced enhanced proliferation and IL-2 release of antigen-specific CD4 1 and CD8 1 T cells compared with BMDC from wild-type mice, in a cell-cell contact manner. The enhanced proliferation by gp49B À/À BMDC was also observed in allogeneic CD4 1 and CD8 1 T cells. Moreover, the transfer of allogeneic BALB/c splenocytes into C57BL/6 gp49B À/À mice induced severe acute graft-versus-host disease with an augmented upregulation of CD86 on CD11c 1 splenic gp49B À/À DC, while transfer of C57BL/6 gp49B À/À splenocytes into BALB/c mice did not, suggesting the exacerbation of the disease was due, at least in part, to augmented activation of recipient gp49B À/À DC. These findings demonstrate a novel regulatory role of gp49B in the function of DC.Key words: Antigen presentation Á Costimulation Á DC Á Regulatory receptor Á Tolerance IntroductionDendritic cells (DC) are professional antigen-presenting cells that recognize a diverse repertoire of antigens and present them to naïve T cells for the induction of acquired immunity [1]. DC are also related to innate immunity by producing cytokines such as both type I and II IFN, or by activating NK cells [2,3]. In addition, recent reports revealed that a subset of DC maintains peripheral tolerance in the steady state [4], showing that DC play a pivotal role in the induction of immune responses including autoimmunity.On the DC surface, a variety of structurally different immunoreceptors that regulate DC and T-cell functions have been found, including CD80, CD86, CD40, and various Ig superfamily and lectin family molecules [5]. Among them, a group of paired Ig superfamily receptors, termed Ig-like receptors, have been attracting the interest of many researchers because they are expressed on various subsets of DC and are considered to contribute to the development or activation of DC [6][7][8][9][10]. Generally, Ig-like receptors are subdivided into two types, namely activating and inhibitory receptors, and in some cases they are expressed on hematopoietic cells in a pair-wise manner [11][12][13][14]. Most activating receptors associate with homodimeric subunits containing ITAM, such as the FcR common g chain and KARAP/DAP12 [15,16], and deliver positive signals into the cells through interaction with their ligands [17]. For instance, the uptake of immune complexes through activating FcR for IgG 2426augments DC maturation, leading to efficient antigen presentation [18...

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“…gp49B has been shown to bind to the integrin a v and b 3 (a v b 3 ), which is expressed on a variety of cells including activated T cells, and this interaction inhibits IgE-dependent degranulation of mast cells (30)(31)(32). Other studies showed that gp49B is also expressed on activated T cells and NK cells, and regulates IFN-g production (32)(33)(34). However, the function of gp49B on any B cell subset has not been determined.…”

mentioning

confidence: 99%

gp49B-Mediated Negative Regulation of Antibody Production by Memory and Marginal Zone B Cells

Fukao

Haniuda

Nojima

et al. 2014

The Journal of Immunology

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The rapid Ab responses observed after primary and secondary immunizations are mainly derived from marginal zone (MZ) and memory B cells, respectively, but it is largely unknown how these responses are negatively regulated. Several inhibitory receptors have been identified and their roles have been studied, but mainly on follicular B cells and much less so on MZ B, and never on memory B cells. gp49B is an Ig superfamily member that contains two ITIMs in its cytoplasmic tail, and it has been shown to negatively regulate mast cell, macrophage, and NK cell responses. In this study, we demonstrate that gp49B is preferentially expressed on memory and MZ B cells. We show that gp49B−/− mice produce more IgM after a primary immunization and more IgM and IgG1 after a secondary immunization than gp49B+/+ mice in T cell–dependent immune responses. Memory and MZ B cells from gp49B−/− mice also produce more Abs upon in vitro stimulation with CD40 than those from gp49B+/+ mice. The in vitro IgM production by MZ B cells from gp49B+/+, but not gp49B−/−, mice is suppressed by interaction with a putative gp49B ligand, the integrin αvβ3 heterodimer. In addition, gp49B−/− mice exhibited exaggerated IgE production in the memory recall response. These results suggest that plasma cell development from memory and MZ B cells, as well as subsequent Ab production, are suppressed via gp49B. In memory B cells, this suppression also prevents excessive IgE production, thus curtailing allergic diseases.

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Inducible Expression of the gp49B Inhibitory Receptor on NK Cells

Cited by 64 publications

References 35 publications

A microarray-based, integrated approach to identify novel regulators of cancer drug response and apoptosis

A microarray-based, integrated approach to identify novel regulators of cancer drug response and apoptosis

A novel regulatory role of gp49B on dendritic cells in T‐cell priming

gp49B-Mediated Negative Regulation of Antibody Production by Memory and Marginal Zone B Cells

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