Mechanism of Induction of NK Activation by 2B4 (CD244) via Its Cognate Ligand

Sinha, Suwan K.; Gao, Ning; Guo, Yuhong; Yuan, Dorothy

doi:10.4049/jimmunol.1002518

Cited by 13 publications

(14 citation statements)

References 28 publications

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“…Surprisingly, however, anti-CD48 immobilized on plastic, can stimulate NK cells to augment their production of cytokines. The activation requires the translocation of CD244 on the same cell [28] suggesting that the stimulation occurs via CD244, which, unlike CD48, can signal via intracellular kinases [29]. There is further indication that the manner of anchoring of CD48 on NK cells differs from that on B cells.…”

Section: Evidence For Nk-cell Regulation Of B-cell Responsesmentioning

confidence: 92%

“…These dramatically opposing functions may be attributed to different splice forms of the transcript that result in alternative intracellular signal transduction [57]. However, the presence of the ligand, CD48, for the receptor, on the same cell may also affect its function depending on the extent of intra vs. intercellular crosslinking that may be modulated by interaction with other cell types that express CD48 [28,[58][59][60]. It is interesting that the cell surface molecule, CD48 is also encoded within the Sle1b locus and a number of reports have indicated NK cell-interactions between CD244 and CD48 expressed on other NK cells as well as on other cell types that may be manifested in functional sequalae [61][62][63].…”

Section: The Role Of Nk Cells In the Production Of Anti-nuclear-antibmentioning

confidence: 96%

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The Role of CD2 Family Members in NK-Cell Regulation of B-Cell Antibody Production

Yuan

2013

Antibodies

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Natural Killer (NK) cells, an important component of the innate immune system, can mount much more rapid responses upon activation than adaptive antigen specific responses. Among the various functions attributed to NK cells their effect on antibody production merits special attention. The modification of IgG subclasses distribution as well as the amplification of the B cell response can be functionally relevant both for mediation of antibody-dependent cellular cytotoxicity (ADCC) and for control of dysregulated autoantibody production. In this review recent experimental evidence for the mechanistic basis of the effect of NK cells on B cell-responses will be covered. Thus, it will be shown that these effects are mediated not only via activation of cytokine and Toll-like receptors (TLR), but also by direct receptor-ligand interactions. Importantly, the function of these receptor/ligands, CD48 and CD244, do not require recognition of class I-MHC molecules but are more dependent on inflammatory conditions brought about by infection or oncogenesis.

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Section: Evidence For Nk-cell Regulation Of B-cell Responsesmentioning

confidence: 92%

Section: The Role Of Nk Cells In the Production Of Anti-nuclear-antibmentioning

confidence: 96%

The Role of CD2 Family Members in NK-Cell Regulation of B-Cell Antibody Production

Yuan

2013

Antibodies

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“…Our previous findings showed that ligation by anti-CD48 can induce the transcription of IL-13 mRNA in IL-2-propagated NK cells and that this stimulation is correlated with a relocation of one of the two ligands for CD48 and CD244, on the same cell [6]. In order to determine if anti-CD48 can stimulate NK cells in vivo, PBLs were isolated on consecutive days after injection of the antibody into B6 mice.…”

Section: Resultsmentioning

confidence: 99%

“…Crosslinking of CD48 on NK cells leads to aggregation of CD244 on the same cell, resulting in phosphorylation of tyrosine residues and subsequent activation of -cytokine production [6]. In vitro experiments utilizing interleukin (IL)-2-propagated NK cells have indicated that stimulation of B cells by NK cells requires the presence of CD48 on B cells and leads to interferon (IFN)-γ-independent activation of downstream exons of the immunoglobulin (Ig) locus as revealed by germline transcriptions [7,8].…”

Section: Introductionmentioning

confidence: 99%

Enhancement of Antigen-Specific Immunoglobulin G Responses by Anti-CD48

Yuan¹,

Guo²,

Thet³

2012

J Innate Immun

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CD48 is a glycosylphosphatidylinositol-anchored protein expressed ubiquitously on many cell types. Despite the poor ability to signal on its own, CD48 can activate cells via interaction with its counter receptors CD2 and CD244 as well as influence the function of other cell surface molecules by costimulatory activities. We show, herein, that injection of anti-CD48 antibodies into mice can augment the antibody response to a T-independent antigen, NP-Ficoll, that is representative of antigenic determinants expressed on the surface of various pathogens, such as Streptococcus pneumoniae. In C57BL/6 mice, enhancement of the response is dependent on natural killer (NK) cells as well as on the presence of CD2 and CD244, ligands for CD48, suggesting a requirement for direct interaction between NK and B cells. Interestingly, in this case, despite a similar augmentation by anti-CD48 in BALB/C mice, the response is independent of NK or T cells, suggesting that help for this response can be derived from other innate cell types. These results provide a pathway by which CD48, when appropriately activated, can influence the course of an antigen-specific antibody response via the innate system.

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“…2B4/CD48 interactions in NK cells are required for the enhanced proliferation and the development of optimal cytolytic and secretory NK effector functions during IL-2 activation [54]. Increased expression of CD48 on the NK cells may allow this ligand to be presented to the 2B4 receptor on opposing NK, T or B cells, thereby priming the NK cells to express IL-13 in the presence of another co-stimulatory signal [55].Human CD97 is a member of the EGF-TM7 family of adhesion class heptahelical receptors and was identified as an early activation marker for human lymphocytes [56]. We observed and validated increased CD97 level in response to IL-2 by real time RT-PCR (Fig.…”

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confidence: 99%

Mining the Immune Cell Proteome to Identify Ovarian Cancer-Specific Biomarkers

Patankar¹

2013

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. REPORT DATE November 2013 REPORT TYPE Final Report DATES COVERED15 PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES)University of Wisconsin-Madison, Madison, WI. 53715 PERFORMING ORGANIZATION REPORT NUMBER SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S) U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for Public Release; Distribution Unlimited SUPPLEMENTARY NOTES 14. ABSTRACT In previous studies we have demonstrated that the ovarian cancer antigen CA125 specifically binds to certain sunsets of immune cell. Based on these observations we have hypothesized that proteomic and transciptomic analysis of immune cells from ovarian cancer patients will result in the identification of specific biomarkers in the immune cells. The current proposal will further investigate this hypothesis by conducting in-depth proteomic analysis of immune cells from cancer patients and healthy blood donors. Studies conducted have resulted in development of streamlined protocols for proteomic analysis of human immune cells. Proteomic analysis of human NK cells has been completed. In addition to proteomic analysis we have also compared the transcriptome of immune cells from ovarian cancer patients and healthy donors and have identified approximately 1600 genes that are differentially expressed in the patient samples. On-going research is focused on validating the proteomic and transcriptome data and demonstrating changes immune cells in response to cancer antigens. iii SUBJECT TERMS IntroductionImmune cells are in continuous crosstalk with tumor cells and other cells in the tumor microenvironment. This crosstalk originates from direct physical contact between the immune cells and the cells in the tumor microenvironment or through their interactions with factors (proteins, lipids and other biomolecules as well as cellular fragments such as exosomes and microparticles) released from the tumors and associated tissues. This interaction causes changes in the molecular make-up of immune cells. In t...

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Mechanism of Induction of NK Activation by 2B4 (CD244) via Its Cognate Ligand

Cited by 13 publications

References 28 publications

The Role of CD2 Family Members in NK-Cell Regulation of B-Cell Antibody Production

The Role of CD2 Family Members in NK-Cell Regulation of B-Cell Antibody Production

Enhancement of Antigen-Specific Immunoglobulin G Responses by Anti-CD48

Mining the Immune Cell Proteome to Identify Ovarian Cancer-Specific Biomarkers

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