title: Intrinsic defect in B-lymphoblastoid cell lines from patients with X-linked lymphoproliferative disease type 1. I. Cell surface phenotype and functional studies.
abstract: BACKGROUND
  Mutations in SH2D1A/DSHP/SAP gene are responsible for the onset of X-linked lymphoproliferative disease type 1 (XLP1) that have increased risk for B-cell lymphoma development. In XLP1 patients SAP deficient NK, NKT and CD8(+) cytotoxic T cells are inefficient in eliminating EBV-infected proliferating B cells that may partially contribute to the lymphoma development. However, little is known about impairment of B cell characteristics in XLP1.
  
  
  OBJECTIVE
  To analyze the cell surface phenotype and functional characteristics of EBV-transformed B-lymphoblastoid cell lines from XLP1 patients (XLP B-LCLs) in comparison with conventional B-lymphoblastoid cell lines (B-LCLs).
  
  
  METHODS
  Studies were performed on SAP-negative B-LCLs T5-1, 6.16, RPMI 1788; SAP-positive B-LCL MP-1 and XLP B-LCLs IARC 739, XLP-D, XLP-8005. Cell surface immunophenotyping was performed using flow cytometry analysis. The level of apoptotic cells (Annexin V-binding), cell viability (MTT assay), and cell proliferation (trypan blue exclusion test) were evaluated in response to ligation of CD40, CD95, CD150 and IgM cell surface receptors.
  
  
  RESULTS
  A cell surface phenotype and functional features that distinguish XLP B-LCLs from conventional B-LCLs were revealed. XLP B-LCLs showed the upregulated level of CD20, CD38 and CD86 cell surface expression and downregulation of CD40, CD80 and CD150 expression. The major functional differences of XLP B-LCLs from conventional B-LCLs concern the modulation of CD95 apoptosis via CD40 and CD150 receptors and unresponsiveness to proliferative signals triggered by CD40 or colligation of BCR with CD150.
  
  
  CONCLUSIONS
  The data suggest that the B-LCL from XLP1 patients have an intrinsic defect that affects cell activation, apoptosis, and proliferation.
authors.affiliation: Department of Cell Regulation, R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology of NAS of Ukraine, Kyiv 03022, Ukraine.
authors.forename: L M
authors.initials: LM
authors.lastname: Shlapatska
authors.affiliation: Department of Cell Regulation, R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology of NAS of Ukraine, Kyiv 03022, Ukraine.
authors.forename: L M
authors.initials: LM
authors.lastname: Kovalevska
authors.affiliation: Department of Cell Regulation, R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology of NAS of Ukraine, Kyiv 03022, Ukraine.
authors.forename: I M
authors.initials: IM
authors.lastname: Gordiienko
authors.affiliation: Department of Cell Regulation, R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology of NAS of Ukraine, Kyiv 03022, Ukraine.
authors.forename: S P
authors.initials: SP
authors.lastname: Sidorenko
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis*; D017209:Apoptosis / Q000235:genetics*; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology*; D002461:Cell Line, Transformed; D049109:Cell Proliferation / Q000235:genetics*; D002470:Cell Survival / Q000235:genetics; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D008232:Lymphoproliferative Disorders / Q000276:immunology* / Q000473:pathology; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D015703:Antigens, CD; D011956:Receptors, Cell Surface