SH2D1A expression in Burkitt lymphoma cells is restricted to EBV positive group I lines and is downregulated in parallel with immunoblastic transformation.
The SH2 domain containing SH2D1A protein has been characterized in relation to the X-linked lymphoproliferative disease (XLP), a primary immunodeficiency that leads to serious clinical conditions after Epstein-Barr virus (EBV) infection. The SH2D1A gene is mutated in the majority of XLP patients. We previously detected SH2D1A in activated T and NK cells, but not in B lymphocytes. We have found SH2D1A protein in Burkitt lymphoma (BL) lines, but only in those that carried EBV and had a Group I (germinal center) phenotype. All the EBV-carrying Group III (immunoblastic) and the EBV-negative BL lines tested were SH2D1A-negative. Motivated by these differences, we studied the impact of EBV and the cellular phenotype on SH2D1A expression. We approached the former question with BL sublines after both the loss of the virus and subsequent reinfection. We also tested original EBV-negative BL lines carrying transfected EBV genes, such as EBNA1, EBNA2, EBNA6, EBER1, 2 and LMP1, respectively. In our experiments, no direct relationship could be seen between EBV and SH2D1A expression. We modified the phenotype of the Group I BL cells by LMP1 transfection or CD40 ligation. The phenotypic changes, indicated by expression of immunoblastic markers, e.g., SLAM, were accompanied by downregulation of SH2D1A. It seems, therefore, that the presence of EBV and the phenotype of the cell together regulate SH2D1A expression in the BL cells. It is possible that SH2D1A is expressed in a narrow window of B cell development represented by germinal center cells.
Microbiology and Tumorbiology Center, Karolinska Institute, Stockholm, Sweden. Noemi.Nagy@mtc.ki.se
Noémi
N
Nagy
Akihiko
A
Maeda
Kentaro
K
Bandobashi
Loránd L
LL
Kis
Jun
J
Nishikawa
Pankaj
P
Trivedi
Alberto
A
Faggioni
George
G
Klein
Eva
E
Klein
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D002051:Burkitt Lymphoma / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D023201:CD40 Ligand / Q000502:physiology; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000378:metabolism; D015536:Down-Regulation; D005434:Flow Cytometry; D004854:Herpesvirus 4, Human / Q000737:chemistry* / Q000502:physiology; D006801:Humans; D015151:Immunoblotting; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D014407:Tumor Cells, Cultured / Q000821:virology; D014763:Viral Matrix Proteins / Q000235:genetics
D002352:Carrier Proteins; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D047908:Intracellular Signaling Peptides and Proteins; C114953:SH2D1A protein, human; C499569:Sh2d1a protein, mouse; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D014763:Viral Matrix Proteins; D023201:CD40 Ligand