A novel membrane antigen selectively expressed on terminally differentiated human B cells

Goto, Tetsuya; Kennel, Stephen J.; Abe, Masahiro; Takishita, Makoto; Kosaka, Masaaki; Solomon, Alan; Saito, Shiro

doi:10.1182/blood.v84.6.1922.1922

Cited by 172 publications

(107 citation statements)

References 38 publications

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“…Our in vivo expression profiling of the antiviral restriction factor and potential tumor-targeting antigen CD317 in nontransformed human organs documented widespread tissue expression on a number of specialized cell types. This stands in contrast to a previous report suggesting selective expression of CD317 on the surface of nontransformed, terminally differentiated B cells (9). Explicitly, that earlier study described a lack of CD317 expression on PBMCs, lymph nodes, liver, spleen, kidney, and heart, applying the identical anti-HM1.24 mAb.…”

Section: Discussioncontrasting

confidence: 99%

“…We suspect that differences in the sensitivity of immunodetection might underlie this discrepancy. Our findings refute the widely held belief that the constitutive expression of CD317 in humans is highly restricted, a misperception that has spurred antibodybased immunotherapy strategies for multiple myeloma and certain solid human tumors (9)(10)(11)(12)(13)(16)(17)(18)(19)(20). In line with our findings, a previous Northern blot analysis documented CD317 mRNA in several tissues, including pancreas, liver, lung, and heart (23).…”

Section: Discussionsupporting

confidence: 88%

“…Based on its apparently selective expression on the surface of terminally differentiated B cells (9), CD317 has been proposed as a therapeutic target for multiple myeloma and related plasma cell-derived immunoproliferative disorders (9)(10)(11)(12)(13). Antibody-based pharmacodelivery approaches are particularly interesting for treatment of chemotherapy-resistant malignancies (14), and the cytotoxicity of anti-CD317 mAbs has been demonstrated in multiple myeloma xenotransplant models (10,15).…”

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confidence: 99%

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In vivo expression profile of the antiviral restriction factor and tumor-targeting antigen CD317/BST-2/HM1.24/tetherin in humans

Erikson

Adam

Schmidt

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Human CD317 is an intrinsic immunity factor that restricts the release of enveloped viruses, including the major pathogens HIV and Lassa virus, from infected cells in culture. Its importance for infection control in humans is unclear, due in part to its incompletely defined in vivo expression pattern. CD317 also has been proposed as a selective target for immunotherapy of multiple myeloma. To provide a framework for studies of the biological functions, regulation, and therapeutic potential of CD317, we performed microarray-based expression profiling in 468 tissue samples from 25 healthy organs from more than 210 patients. We found that CD317 protein was expressed to varying degrees in all organs tested and detected in a number of specialized cell types, including hepatocytes, pneumocytes, ducts of major salivary glands, pancreas and kidney, Paneth cells, epithelia, Leydig cells, plasma cells, bone marrow stromal cells, monocytes, and vascular endothelium. Although many of these cell types are in vivo targets for pathogenic viruses, restriction by CD317 or virus-encoded antagonists has been documented in only some of them. Limited cell type–dependent coexpression of CD317 with the IFN biomarker MxA in vivo and lack of responsive stimulation in organ explants suggest that interferons may only partially regulate CD317. This in vivo expression profiling sheds light on the biology and species-specificity of CD317, identifies multiple thus far unknown interaction sites of viruses with this restriction factor, and refutes the concept of its restricted constitutive expression and primary IFN inducibility. CD317's widespread expression calls into question its suitability as a target for immunotherapy.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionsupporting

confidence: 88%

mentioning

confidence: 99%

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In vivo expression profile of the antiviral restriction factor and tumor-targeting antigen CD317/BST-2/HM1.24/tetherin in humans

Erikson

Adam

Schmidt

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…The MM cells were prepared from bone marrow mononuclear cells obtained from patients by a negative selection using immunomagnetic beads with a cocktail of monoclonal antibodies against CD3, CD4, CD8, CD19, CD11b, CD14, CD16 and CD33 followed by a positive selection with a human MM cell-specific anti-HM1.24 monoclonal antibody, raised in our laboratory as described previously (Goto et al, 1994;Ozaki et al, 1997). The purity of isolated myeloma cells was more than 95%.…”

Section: Isolation Of Primary MM Cellsmentioning

confidence: 99%

Ability of myeloma cells to secrete macrophage inflammatory protein (MIP)‐1α and MIP‐1β correlates with lytic bone lesions in patients with multiple myeloma

et al. 2004

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“…Bone marrow stromal antigen 2 (BST-2; also known as CD317 or tetherin) was initially identified to be a pre-B-cell growth promoter (17,18). However, BST-2 is also a marker of type I interferon-producing cells (IPC) and is broadly expressed in many cell types when treated with type I interferon (19).…”

mentioning

confidence: 99%

Severe Acute Respiratory Syndrome Coronavirus ORF7a Inhibits Bone Marrow Stromal Antigen 2 Virion Tethering through a Novel Mechanism of Glycosylation Interference

Taylor

Coleman

Postel

et al. 2015

J Virol

147

158

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Severe acute respiratory syndrome (SARS) emerged in November 2002 as a case of atypical pneumonia in China, and the causative agent of SARS was identified to be a novel coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV). Bone marrow stromal antigen 2 (BST-2; also known as CD317 or tetherin) was initially identified to be a pre-B-cell growth promoter, but it also inhibits the release of virions of the retrovirus human immunodeficiency virus type 1 (HIV-1) by tethering budding virions to the host cell membrane. Further work has shown that BST-2 restricts the release of many other viruses, including the human coronavirus 229E (hCoV-229E), and the genomes of many of these viruses encode BST-2 antagonists to overcome BST-2 restriction. Given the previous studies on BST-2, we aimed to determine if BST-2 has the ability to restrict SARS-CoV and if the SARS-CoV genome encodes any proteins that modulate BST-2's antiviral function. Through an in vitro screen, we identified four potential BST-2 modulators encoded by the SARS-CoV genome: the papain-like protease (PL Pro ), nonstructural protein 1 (nsp1), ORF6, and ORF7a. As the function of ORF7a in SARS-CoV replication was previously unknown, we focused our study on ORF7a. We found that BST-2 does restrict SARS-CoV, but the loss of ORF7a leads to a much greater restriction, confirming the role of ORF7a as an inhibitor of BST-2. We further characterized the mechanism of BST-2 inhibition by ORF7a and found that ORF7a localization changes when BST-2 is overexpressed and ORF7a binds directly to BST-2. Finally, we also show that SARSCoV ORF7a blocks the restriction activity of BST-2 by blocking the glycosylation of BST-2. IMPORTANCEThe severe acute respiratory syndrome coronavirus (SARS-CoV) emerged from zoonotic sources in 2002 and caused over 8,000 infections and 800 deaths in 37 countries around the world. Identifying host factors that regulate SARS-CoV pathogenesis is critical to understanding how this lethal virus causes disease. We have found that BST-2 is capable of restricting SARS-CoV release from cells; however, we also identified a SARS-CoV protein that inhibits BST-2 function. We show that the SARS-CoV protein ORF7a inhibits BST-2 glycosylation, leading to a loss of BST-2's antiviral function. Severe acute respiratory syndrome coronavirus (SARS-CoV) was identified to be the causative agent of a 2002 to 2004 outbreak of severe respiratory disease that emerged from the Guangdong province of China, resulting in 8,096 cases and 774 deaths across 37 countries (1, 2). SARS-CoV is an enveloped virus with a positive-sense, single-stranded RNA genome of roughly 30,000 nucleotides encoding four structural proteins: the spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins (3). N protein forms the nucleocapsid, while E and M are minor virion membrane proteins. SARS-CoV entry into the cell is mediated by S-protein binding to angiotensin-converting enzyme 2 (ACE2) on the cell surface (4). In addition to the structural proteins, the SARS-C...

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A novel membrane antigen selectively expressed on terminally differentiated human B cells

Cited by 172 publications

References 38 publications

In vivo expression profile of the antiviral restriction factor and tumor-targeting antigen CD317/BST-2/HM1.24/tetherin in humans

In vivo expression profile of the antiviral restriction factor and tumor-targeting antigen CD317/BST-2/HM1.24/tetherin in humans

Ability of myeloma cells to secrete macrophage inflammatory protein (MIP)‐1α and MIP‐1β correlates with lytic bone lesions in patients with multiple myeloma

Severe Acute Respiratory Syndrome Coronavirus ORF7a Inhibits Bone Marrow Stromal Antigen 2 Virion Tethering through a Novel Mechanism of Glycosylation Interference

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