Epstein-Barr virus LMP2A drives B cell development and survival in the absence of normal B cell receptor signals.
Epstein-Barr virus (EBV) establishes a persistent latent infection in peripheral B lymphocytes in humans and is associated with a variety of malignancies and proliferative disorders. Latent membrane protein 2A (LMP2A) is one of only two viral proteins expressed in latently infected B lymphocytes in vivo. LMP2A blocks B cell receptor (BCR) signal transduction in vitro by binding the Syk and Lyn protein tyrosine kinases. To analyze the significance of LMP2A expression in vivo, transgenic mice with B cell lineage expression of LMP2A were generated. LMP2A expression results in the bypass of normal B lymphocyte developmental checkpoints allowing immunoglobulin-negative cells to colonize peripheral lymphoid organs, indicating that LMP2A possesses a constitutive signaling activity in nontransformed cells.
Caldwell
R G
RG
Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Wilson
J B
JB
Anderson
S J
SJ
Longnecker
R
R
D000818:Animals; D030801:Animals, Genetically Modified; D001402:B-Lymphocytes / Q000166:cytology* / Q000821:virology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D002454:Cell Differentiation; D002470:Cell Survival; D002478:Cells, Cultured; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain / Q000187:drug effects / Q000502:physiology; D016654:Genes, RAG-1 / Q000502:physiology; D004854:Herpesvirus 4, Human / Q000737:chemistry* / Q000276:immunology*; D015851:Interleukin-7 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D015398:Signal Transduction; D019076:Transgenes / Q000502:physiology; D014763:Viral Matrix Proteins / Q000235:genetics / Q000502:physiology*
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D015851:Interleukin-7; D011947:Receptors, Antigen, B-Cell; D014763:Viral Matrix Proteins