Ly108: a new member of the mouse CD2 family of cell surface proteins

Peck, Susan; Ruley, H E

doi:10.1007/s002510000252

Cited by 42 publications

(30 citation statements)

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“…Finally, we determined the expression level of CD43 and Ly108, whereby Ly108 is a membrane glycoprotein of the SLAM family that, as opposed to CD43, is down-regulated with NK-cell maturation. 6,36,37 As expected, CD43 expression was highest and Ly108 was lowest on the most functionally mature CD27 Ϫ NK-cell subset relative to the CD27 ϩ NK-cell subset ( Figure 3C). In contrast, B220 ϩ NK cells exhibited the lowest level of CD43 and the highest level of Ly108 in comparison to both CD27 ϩ and CD27 Ϫ NK cells, as observed in both C57BL/6 and B6.Rag1 Ϫ/Ϫ mice ( Figure 3C).…”

supporting

confidence: 77%

Redefining interferon-producing killer dendritic cells as a novel intermediate in NK-cell differentiation

Guimont-Desrochers

Boucher

Dong

et al. 2012

Blood

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The cell lineage origin of IFN-producing killer dendritic cells (IKDCs), which exhibit prominent antitumoral activity, has been subject to debate. Although IKDCs were first described as a cell type exhibiting both plasmacytoid DC and natural killer (NK) cell properties, the current view reflects that IKDCs merely represent activated NK cells expressing B220, which were thus renamed B220 ؉ NK cells. Herein, we further investigate the lineage relation of B220 ؉ NK cells with regard to other NK-cell subsets. We surprisingly find that, after adoptive transfer, B220 ؊ NK cells did not acquire B220 expression, even in the presence of potent activating stimuli. These findings strongly argue against the concept that B220 IntroductionNatural killer (NK) cells are large granular lymphocytes that were first described for their capacity to spontaneously eliminate tumor cells and virus-infected cells without prior sensitization. 1 These functions are mediated by an array of Ig-like and C-type lectin receptors that deliver both activating and inhibitory signals. 1 In addition to their cytotoxic activity, NK cells rapidly produce vast amounts of cytokines, such as IFN-␥, as well as other cellular mediators, including chemokines. NK cells thus act as an important first line of defense in the early control of virus infection, in tumor immunosurveillance, and in immunoregulation.The differentiation of NK cells from hematopoietic stem cells in the BM is incompletely understood, but it is thought to occur in a sequential manner that involves multiple stages of development that is based on phenotype, function, and turnover. 2 The first committed NK-cell precursor (NKP) is characterized by CD122 ϩ expression in the absence of the expression of other lineage markers, 3 although a pre-NKP cell lacking CD122 expression has recently been characterized as a NK cell-committed progenitor preceding NKP in the differentiation stages. 4 NKPs subsequently give rise to immature NK (iNK) cells that express CD122 along with NK1.1 and CD94/NKG2. As iNK cells differentiate further, they undergo education to achieve their full functional competence, and they acquire CD49b expression to finally become mature NK (mNK) cells. 2 These CD49b ϩ mNK cells still compose a heterogeneous cell population that may be segregated according to their phenotype, function, and tissue distribution. Indeed, functional maturation of CD49b ϩ mNK cells proceeds along 4 stages from the CD11b Ϫ CD27 Ϫ to the CD11b Ϫ CD27 ϩ then to the CD11b ϩ CD27 ϩ and finally to the CD11b ϩ CD27 Ϫ subset. 5 Several other markers are acquired along this differentiation process, including CD43, CD94-NKG2, and Ly49 receptors. [5][6][7] Finally, on activation, mNK cells gain the expression of additional activation markers, namely CD69, CD44, FasL, CD86, and MHC II. [8][9][10][11][12] In addition, activated mNK cells increase in size and show heightened functional properties such as an enhanced cytolytic potential and increased ability to produce cytokines. 2 Notably, activated mNK cells show ...

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confidence: 77%

Redefining interferon-producing killer dendritic cells as a novel intermediate in NK-cell differentiation

Guimont-Desrochers

Boucher

Dong

et al. 2012

Blood

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“…21 In accordance with these results, we observed expression of CD229 on a variety of myeloma cell lines. Members of the SLAM family of molecules other than CD229 have previously been suggested to be expressed on normal B cells [25][26][27][28][29][30][31] and SLAM family member CS-1 has also been detected on malignant plasma cells. 32 However, our findings indicate that CD229 is the SLAM family member with the highest potential for the development of myeloma-targeting therapies because: (i) CD229 showed the broadest expression of all SLAM members on myeloma cell lines and (ii) CD229 seems to have the most tumor-restricted expression of all SLAM members.…”

Section: Discussionmentioning

confidence: 99%

Surface molecule CD229 as a novel target for the diagnosis and treatment of multiple myeloma

Atanackovic¹,

Panse²,

Hildebrandt³

et al. 2011

Haematologica

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The online version of this article has a Supplementary Appendix. BackgroundTo date, multiple myeloma remains an incurable malignancy due to the persistence of minimal residual disease in the bone marrow. In this setting, monoclonal antibodies against myelomaspecific cell surface antigens represent a promising therapeutic approach, which is however hampered by a lack of appropriate target structures expressed across all pathogenic myeloma cell populations. We, therefore, investigated functionally relevant immunoreceptors specifically associated with myeloma cells as well as their clonogenic precursors. Design and MethodsPotential target proteins were identified using antibody arrays against phosphorylated immunoreceptors with lysates from myeloma cell lines. CD229 expression was confirmed in primary myeloma cells by reverse transcriptase polymerase chain reaction, western blot, fluorescence-activated cell sorting, and immunohistochemistry. Apoptosis, clonogenic growth, and sensitivity to chemotherapy were determined following short-interfering RNA-mediated downregulation of CD229. Antibody-dependent cellular and complement-dependent cytotoxicity were analyzed using a monoclonal antibody against CD229 to demonstrate the antigen's immunotherapeutic potential. ResultsOur screening assay identified CD229 as the most strongly over-expressed/phosphorylated immunoreceptor in myeloma cell lines. Over-expression was further demonstrated in the CD138-negative population, which has been suggested to represent myeloma precursors, as well as on primary tumor cells from myeloma patients. Accordingly, CD229 staining of patients' bone marrow samples enabled the identification of myeloma cells by flow cytometry and immunohistochemistry. Down-regulation of CD229 led to a decreased number of viable myeloma cells and clonal myeloma colonies, and enhanced the anti-tumor activity of conventional chemotherapeutics. Targeting CD229 with a monoclonal antibody resulted in complement-and cell-mediated lysis of myeloma cells. ConclusionsOur results demonstrate that the immunoreceptor CD229 is specifically over-expressed on myeloma cells including their clonogenic precursors and contributes to their malignant phenotype. Monoclonal antibodies against this protein may represent a promising diagnostic and immunotherapeutic instrument in this disease. Haematologica 2011;96(10):1512-1520. doi:10.3324/haematol.2010 Surface molecule CD229 as a novel target for the diagnosis and treatment of multiple myeloma

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“…1,2 It is a member of the immunoglobulin superfamily and shares homology with CD84, CD229, CD244, CD48, CD2, 19A, and Ly108. 3 CD150 was recently shown to be the second receptor for measles virus in addition to CD46. [4][5][6][7] CD150 is a self-ligand 8,9 with diverse immunologic functions including T/B-cell costimulation, 1,10,11 induction of interferon ␥ (IFN-␥) in Th1 T-cell clones, redirection of Th2 clones to a Th1 or Th0 phenotype, [12][13][14] and inhibition of apoptosis in B cells.…”

Section: Introductionmentioning

confidence: 99%

Molecular dissection of the signaling and costimulatory functions of CD150 (SLAM): CD150/SAP binding and CD150-mediated costimulation

Howie

Simarro

Sayós

et al. 2002

Blood

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Ly108: a new member of the mouse CD2 family of cell surface proteins

Cited by 42 publications

References 0 publications

Redefining interferon-producing killer dendritic cells as a novel intermediate in NK-cell differentiation

Redefining interferon-producing killer dendritic cells as a novel intermediate in NK-cell differentiation

Surface molecule CD229 as a novel target for the diagnosis and treatment of multiple myeloma

Molecular dissection of the signaling and costimulatory functions of CD150 (SLAM): CD150/SAP binding and CD150-mediated costimulation

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