scholarly journals Association of killer cell immunoglobulin-like receptors with endemic Burkitt lymphoma in Kenyan children

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Beatrice M. Muriuki ◽  
Catherine S. Forconi ◽  
Peter O. Oluoch ◽  
Jeffrey A. Bailey ◽  
Anita Ghansah ◽  
...  
Keyword(s):  
Nk Cells ◽  
Burkitt Lymphoma ◽  
Nk Cell ◽  
Killer Cell ◽  
B Cell Lymphoma ◽  
Kir Genes ◽  
Barr Virus ◽  
Equatorial Africa ◽  
Epstein Barr ◽  
Allelic Variations

AbstractEndemic Burkitt lymphoma (eBL) is an aggressive pediatric B cell lymphoma, common in Equatorial Africa. Co-infections with Epstein-Barr virus (EBV) and Plasmodium falciparum, coupled with c-myc translocation are involved in eBL etiology. Infection-induced immune evasion mechanisms to avoid T cell cytotoxicity may increase the role of Natural killer (NK) cells in anti-tumor immunosurveillance. Killer immunoglobulin-like receptor (KIR) genes on NK cells exhibit genotypic and allelic variations and are associated with susceptibility to diseases and malignancies. However, their role in eBL pathogenesis remains undefined. This retrospective study genotyped sixteen KIR genes and compared their frequencies in eBL patients (n = 104) and healthy geographically-matched children (n = 104) using sequence-specific primers polymerase chain reaction (SSP-PCR) technique. The relationship between KIR polymorphisms with EBV loads and eBL pathogenesis was investigated. Possession of ≥ 4 activating KIRs predisposed individuals to eBL (OR = 3.340; 95% CI 1.530–7.825; p = 0.004). High EBV levels were observed in Bx haplogroup (p = 0.016) and AB genotypes (p = 0.042) relative to AA haplogroup and AA genotype respectively, in eBL patients but not in healthy controls. Our results suggest that KIR-mediated NK cell stimulation could mute EBV control, contributing to eBL pathogenesis.

scholarly journals Association of Killer Cell Immunoglobulin-Like Receptors With Endemic Burkitt Lymphoma in Kenyan Children

2021 ◽  
Author(s):  
Beatrice Muriuki ◽  
Catherine Forconi ◽  
Peter Oluoch ◽  
Jeffrey Bailey ◽  
Anita Ghansah ◽  
...  
Keyword(s):  
Nk Cells ◽  
Burkitt Lymphoma ◽  
Nk Cell ◽  
Killer Cell ◽  
B Cell Lymphoma ◽  
Kir Genes ◽  
Barr Virus ◽  
Equatorial Africa ◽  
Epstein Barr ◽  
Allelic Variations

Abstract Endemic Burkitt lymphoma (eBL) is an aggressive pediatric B cell lymphoma, common in Equatorial Africa. Co-infections with Epstein-Barr virus (EBV) and Plasmodium falciparum, coupled with c-myc translocation are involved in eBL etiology. Infection-induced immune evasion mechanisms to avoid T cell cytotoxicity may increase the role of Natural killer (NK) cells in anti-tumor immunosurveillance. Killer immunoglobulin-like receptor (KIR) genes on NK cells exhibit genotypic and allelic variations and are associated with susceptibility to diseases and malignancies. However, their role in eBL pathogenesis remains undefined. This retrospective study genotyped sixteen KIR genes and compared their frequencies in eBL patients (n=104) and healthy geographically-matched children (n=104) using sequence-specific primers polymerase chain reaction (SSP-PCR) technique. The relationship between KIR polymorphisms with EBV loads and eBL pathogenesis was investigated. Possession of ≥4 activating KIRs predisposed individuals to eBL (OR=3.340; 95% CI 1.530-7.825; p=0.004). High EBV levels were observed in Bx haplogroup (p=0.016) and AB genotypes (p=0.049) relative to AA haplogroup and AA genotype respectively, in eBL patients but not in healthy controls. Our results suggest that KIR- mediated NK cell stimulation could mute EBV control, contributing to eBL pathogenesis.

scholarly journals Natural Killer Cell Responses during Human γ-Herpesvirus Infections

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 655
Author(s):  
Christian Münz
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Epstein Barr Virus ◽  
Nk Cell ◽  
Killer Cell ◽  
Kaposi Sarcoma ◽  
Antibody Dependent Cellular Cytotoxicity ◽  
Barr Virus ◽  
Cell Responses ◽  
Epstein Barr

Herpesviruses are main sculptors of natural killer (NK) cell repertoires. While the β-herpesvirus human cytomegalovirus (CMV) drives the accumulation of adaptive NKG2C-positive NK cells, the human γ-herpesvirus Epstein–Barr virus (EBV) expands early differentiated NKG2A-positive NK cells. While adaptive NK cells support adaptive immunity by antibody-dependent cellular cytotoxicity, NKG2A-positive NK cells seem to preferentially target lytic EBV replicating B cells. The importance of this restriction of EBV replication during γ-herpesvirus pathogenesis will be discussed. Furthermore, the modification of EBV-driven NK cell expansion by coinfections, including by the other human γ-herpesvirus Kaposi sarcoma-associated herpesvirus (KSHV), will be summarized.

scholarly journals Reduced frequency of cytotoxic CD56dim CD16+ NK cells leads to impaired antibody-dependent degranulation in EBV-positive classical Hodgkin lymphoma

2021 ◽  
Author(s):  
Elena Pánisová ◽  
Anna Lünemann ◽  
Simone Bürgler ◽  
Monika Kotur ◽  
Julien Lazarovici ◽  
...  
Keyword(s):  
Nk Cells ◽  
Hodgkin Lymphoma ◽  
Nk Cell ◽  
Cell Subset ◽  
Adjunctive Treatment ◽  
Classical Hodgkin Lymphoma ◽  
Barr Virus ◽  
Class 1 ◽  
Epstein Barr

AbstractAround 30–50% of classical Hodgkin lymphoma (cHL) cases in immunocompetent individuals from industrialized countries are associated with the B-lymphotropic Epstein-Barr virus (EBV). Although natural killer (NK) cells exhibit anti-viral and anti-tumoral functions, virtually nothing is known about quantitative and qualitative differences in NK cells in patients with EBV+ cHL vs. EBV- cHL. Here, we prospectively investigated 36 cHL patients without known immune suppression or overt immunodeficiency at diagnosis. All 10 EBV+ cHL patients and 25 out 26 EBV- cHL were seropositive for EBV antibodies, and EBV+ cHL patients presented with higher plasma EBV DNA levels compared to EBV- cHL patients. We show that the CD56dim CD16+ NK cell subset was decreased in frequency in EBV+ cHL patients compared to EBV- cHL patients. This quantitative deficiency translates into an impaired CD56dim NK cell mediated degranulation toward rituximab-coated HLA class 1 negative lymphoblastoid cells in EBV+ compared to EBV- cHL patients. We finally observed a trend to a decrease in the rituximab-associated degranulation and ADCC of in vitro expanded NK cells of EBV+ cHL compared to healthy controls. Our findings may impact on the design of adjunctive treatment targeting antibody-dependent cellular cytotoxicity in EBV+ cHL.

scholarly journals Epstein–Barr virus peptides derived from latent cycle proteins alter NKG2A + NK cell effector function

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Berenice Mbiribindi ◽  
Josselyn K. Pena ◽  
Matthew P. Arvedson ◽  
Claudia Moreno Romero ◽  
Sarah R. McCarthy ◽  
...  
Keyword(s):  
Nk Cells ◽  
Epstein Barr Virus ◽  
Cell Activation ◽  
Nk Cell ◽  
Human Leukocyte ◽  
Effector Function ◽  
Barr Virus ◽  
Epstein Barr ◽  
Cell Effector Function ◽  
Cell Effector

AbstractNatural killer (NK) cells control viral infection through the interaction between inhibitory receptors and human leukocyte antigen (HLA) ligands and bound peptide. NK cells expressing the inhibitory receptor NKG2A/CD94 recognize and respond to autologous B cells latently infected with Epstein–Barr virus (EBV). The mechanism is not yet understood, thus we investigated peptides derived from seven latent proteins of EBV in the interaction of NKG2A and its ligand HLA-E. Functional analysis demonstrated that EBV peptides can bind to HLA-E and block inhibition of NK cell effector function. Moreover, analysis of DNA from 79 subjects showed sequence variations in the latent protein, LMP1, which alters NK responses to EBV. We provide evidence that peptides derived from EBV latent cycle proteins can impair the recognition of NKG2A despite being presented by HLA-E, resulting in NK cell activation.

scholarly journals Genetic Subgroups Inform on Pathobiology in Adult and Pediatric Burkitt Lymphoma

2021 ◽  
Author(s):  
Nicole Thomas ◽  
Kostiantyn Dreval ◽  
Daniela S. Gerhard ◽  
Laura K. Hilton ◽  
Jeremy S. Abramson ◽  
...  
Keyword(s):  
Burkitt Lymphoma ◽  
Somatic Hypermutation ◽  
B Cell Lymphoma ◽  
Epidemiological Studies ◽  
Sub Saharan Africa ◽  
Driver Mutations ◽  
Barr Virus ◽  
Molecular Features ◽  
Genetic Features ◽  
Epstein Barr

AbstractBurkitt lymphoma (BL) accounts for the majority of pediatric non-Hodgkin lymphomas (NHL) and is relatively rare but significantly more lethal when diagnosed in adults. The global incidence is highest in Sub-Saharan Africa, where Epstein-Barr virus (EBV) positivity is observed in 95% of all tumors. Both pediatric (pBL) and adult (aBL) cases are known to share some driver mutations, for example MYC translocations, which are seen in > 90% of cases. Sequencing efforts have identified many common somatic alterations that cooperate with MYC in lymphomagenesis with approximately 30 significantly mutated genes (SMG) reported thus far. Recent analyses revealed non-coding mutation patterns in pBL that were attributed to aberrant somatic hypermutation (aSHM). We sought to identify genomic and molecular features that may explain clinical disparities within and between aBL and pBL in an effort to delineate BL subtypes that may allow for the stratification of patients with shared pathobiology. Through comprehensive sequencing of BL genomes, we found additional SMGs, including more genetic features that associate with tumor EBV status, and established three new genetic subgroups that span pBL and aBL. Direct comparisons between pBL and aBL revealed only marginal differences and the mutational profiles were consistently better explained by EBV status. Using an unsupervised clustering approach to identify subgroupings within BL and diffuse large B-cell lymphoma (DLBCL), we have defined three genetic subgroups that predominantly comprise BL tumors. Akin to the recently defined DLBCL subgroups, each BL subgroup is characterized by combinations of common driver mutations and non-coding mutations caused by aSHM. Two of these subgroups and their prototypical genetic features (ID3 and TP53) had significant associations with patient outcomes that were different among the aBL and pBL cohorts. These findings highlight not only a shared pathogenesis between aBL and pBL, but also establish genetic subtypes within BL that serve to delineate tumors with distinct molecular features, providing a new framework for epidemiological studies, and diagnostic and therapeutic strategies.

Natural Killer Cell Precursor Acute Lymphoma/Leukemia Presenting in an Infant

2001 ◽  
Vol 125 (3) ◽  
pp. 413-418
Author(s):  
Yasodha Natkunam ◽  
Athena M. Cherry ◽  
P. Joanne Cornbleet
Keyword(s):  
Natural Killer ◽  
Nk Cell ◽  
Killer Cell ◽  
Cell Precursor ◽  
Barr Virus ◽  
Hla Dr ◽  
Blue Cell ◽  
Epstein Barr ◽  
Round Blue Cell Tumor ◽  
Hematolymphoid Neoplasms

Abstract Lymphoma/leukemia derived from immature natural killer (NK) cells occur most commonly in adults and are characterized by blastic cytologic features and an aggressive outcome. Predilection for extranodal sites and absence of the Epstein-Barr virus associated with mature NK cell malignancies further distinguish this entity. We present a NK precursor acute lymphoma presenting with multiple masses in an infant without circulating blasts or marrow replacement by disease. The diagnostic difficulty arose from several factors, including young age, presentation with multiple masses, blastic cytologic features mistaken for a small, round, blue cell tumor, and the absence of lineage-specific markers. The CD56+, CD34+, CD33+, MPO−, cytoplasmic CD3+, CD45−, CD7−, HLA-DR−, and TdT− immunophenotype of this neoplasm overlaps with previously reported cases of myeloid/NK precursor acute leukemia and blastic NK cell lymphoma/leukemia. This case emphasizes the need for a strong index of suspicion to recognize this rare entity and to distinguish it from solid tumors and other hematolymphoid neoplasms that occur in infancy.

A role for Blimp1 in the transcriptional network controlling natural killer cell maturation

Blood ◽  
2011 ◽  
Vol 117 (6) ◽  
pp. 1869-1879 ◽  
Author(s):  
Axel Kallies ◽  
Sebastian Carotta ◽  
Nicholas D. Huntington ◽  
Nicholas J. Bernard ◽  
David M. Tarlinton ◽  
...  
Keyword(s):  
T Cells ◽  
Nk Cells ◽  
Natural Killer ◽  
Cytokine Production ◽  
Plasma Cells ◽  
Nk Cell ◽  
Killer Cell ◽  
B Cell Lymphoma ◽  
Cell Maturation ◽  
Proliferative Potential

Abstract Natural killer (NK) cells are innate lymphocytes capable of immediate effector functions including cytokine production and cytotoxicity. Compared with B and T cells, the factors that control the peripheral maturation of NK cells are poorly understood. We show that Blimp1, a transcriptional repressor required for the differentiation of plasma cells and short-lived effector T cells, is expressed by NK cells throughout their development. Interleukin 15 (IL-15) is required for the early induction of Blimp1 in NK cells, with expression increasing in the most mature subsets of mouse and human NK cells. We show that Blimp1 is required for NK-cell maturation and homeostasis and for regulating their proliferative potential. It is also essential for high granzyme B expression, but not for most cytokine production and cytotoxicity. Surprisingly, interferon regulatory factor 4 (IRF4) and B-cell lymphoma 6 (Bcl6), 2 transcription factors crucial for the regulation of Blimp1 in B and T cells, are largely dispensable for Blimp1 expression in NK cells. T-bet deficiency, however, leads to attenuated Blimp1 expression. We have identified NK cells as the first hematopoietic cell type in which the IRF4-Blimp1-Bcl6 regulatory axis is not in operation, highlighting the distinct nature of the NK-cell gene-regulatory network.

scholarly journals Epstein-Barr Virus-Induced Gene 3 (EBI3): A Novel Diagnosis Marker in Burkitt Lymphoma and Diffuse Large B-Cell Lymphoma

PLoS ONE ◽  
2011 ◽  
Vol 6 (9) ◽  
pp. e24617 ◽  
Author(s):  
Julie Gonin ◽  
Frédérique Larousserie ◽  
Christian Bastard ◽  
Jean-Michel Picquenot ◽  
Jérôme Couturier ◽  
...  
Keyword(s):  
B Cell ◽  
Burkitt Lymphoma ◽  
Epstein Barr Virus ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Barr Virus ◽  
Large B Cell Lymphoma ◽  
Epstein Barr ◽  
Large B Cell

scholarly journals NKB1: a natural killer cell receptor involved in the recognition of polymorphic HLA-B molecules.

1994 ◽  
Vol 180 (2) ◽  
pp. 537-543 ◽  
Author(s):  
V Litwin ◽  
J Gumperz ◽  
P Parham ◽  
J H Phillips ◽  
L L Lanier
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Cell Clone ◽  
Killer Cell ◽  
Cell Receptor ◽  
Target Cells ◽  
Multiple Alleles ◽  
Barr Virus ◽  
Cell Clones

Natural killer (NK) cells kill normal and transformed hematopoietic cells that lack expression of major histocompatibility complex (MHC) class I antigens. Lysis of HLA-negative Epstein Barr virus-transformed B lymphoblastoid cell lines (B-LCL) by human NK cell clones can be inhibited by transfection of the target cells with certain HLA-A, -B, or -C alleles. NK cell clones established from an individual demonstrate clonal heterogeneity in HLA recognition and a single NK clone can recognize multiple alleles. We describe a potential human NK cell receptor (NKB1) for certain HLA-B alleles (e.g., HLA-B*5101 and-B*5801) identified by the mAb DX9. NKB1 is a 70-kD glycoprotein that is expressed on a subset of NK cells and NK cell clones. DX9 monoclonal antibody (mAb) specifically inhibits the interaction between NK cell clones and B-LCL targets transfected with certain HLA-B alleles, but does not affect recognition of HLA-A or HLA-C antigens. An individual NK cell clone can independently recognize B-LCL targets transfected with HLA-B or HLA-C antigens; however, DX9 mAb only affects interaction with transfectants expressing certain HLA-B alleles. These findings demonstrate the existence of NK cell receptors involved in the recognition of HLA-B and imply the presence of multiple receptors for MHC on an individual NK clone.

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