title: Induction of latent membrane protein expression in in vitro Epstein-Barr virus-infected leukaemic B lymphocytes by interleukin 4 and antibodies to CD40.
abstract: Chronic lymphocytic leukaemia (CLL) B cells are clones representing the mature B cell phenotype. On infection with Epstein-Barr virus (EBV) CLL cells express the EB nuclear antigen (EBNA) complex but unlike EBV-infected normal B cells they do not express LMP nor do they proliferate or immortalize. Furthermore, EBV-CLL rapidly die by apoptosis in culture. In the present study we have used the B cell growth factors interleukin 4 and antibodies to CD40 to induce activation and proliferation of EBV-infected CLL cells. Although cell numbers did not significantly increase, apoptosis was partially inhibited in CLL cells which expressed increased levels of CD23 and were activated to immunoglobulin-secreting lymphoblasts. Expression of LMP was induced by interleukin (IL)-4 and anti-CD40 in all five EBV-infected CLL samples examined. However, this did not enhance cell proliferation or induce immortalization. Further analysis showed that LMP could be detected 4-5 days after EBV infection, and that both IL-4 and anti-CD40 could independently induce LMP but that their effect was additive. These results indicate that LMP expression is dependent on B cell activation processes and that in some circumstances full latent viral gene expression is not sufficient to cause B cell immortalization.
authors.affiliation: Department of Clinical Sciences, London School of Hygiene and Tropical Medicine, UK.
authors.forename: D H
authors.initials: DH
authors.lastname: Crawford
authors.forename: J A
authors.initials: JA
authors.lastname: Thomas
authors.forename: C D
authors.initials: CD
authors.lastname: Gregory
authors.forename: D
authors.initials: D
authors.lastname: Catovsky
authors.forename: K
authors.initials: K
authors.lastname: Chaggar
mesh_terms: D000906:Antibodies / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001402:B-Lymphocytes / Q000187:drug effects* / Q000473:pathology / Q000821:virology*; D019013:CD40 Antigens; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002472:Cell Transformation, Viral; D015870:Gene Expression / Q000187:drug effects; D006566:Herpesviridae Infections / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000821:virology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology; D014407:Tumor Cells, Cultured; D014412:Tumor Virus Infections / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D014763:Viral Matrix Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D000906:Antibodies; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins; D015847:Interleukin-4; D006854:Hydrocortisone