Mimicry of CD40 signals by Epstein-Barr virus LMP1 in B lymphocyte responses.
The effect of the Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) on the activation and differentiation of normal B cells was investigated. B cells of transgenic mice expressing LMP1 under the control of immunoglobulin promoter/enhancer displayed enhanced expression of activation antigens and spontaneously proliferated and produced antibody. Humoral immune responses of LMP1 transgenic mice in CD40-deficient or normal backgrounds revealed that LMP1 mimics CD40 signals to induce extrafollicular B cell differentiation but, unlike CD40, blocks germinal center formation. Thus, these specific properties of LMP1 may determine the site of primary B cell infection and the state of infection in the natural course of EBV infection, whereas subsequent loss of LMP1 expression may affect the site of persistent latent infection.
Uchida
J
J
Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
Yasui
T
T
Takaoka-Shichijo
Y
Y
Muraoka
M
M
Kulwichit
W
W
Raab-Traub
N
N
Kikutani
H
H
D000818:Animals; D000915:Antibody Affinity; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D019013:CD40 Antigens / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D005260:Female; D018858:Germinal Center / Q000276:immunology / Q000378:metabolism; D004854:Herpesvirus 4, Human / Q000378:metabolism* / Q000502:physiology; D007114:Immunization; D017578:Immunoglobulin Class Switching; D007136:Immunoglobulins / Q000096:biosynthesis; D015847:Interleukin-4 / Q000494:pharmacology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018716:Molecular Mimicry; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction; D013154:Spleen / Q000276:immunology; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism*
D019013:CD40 Antigens; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D007136:Immunoglobulins; D016328:NF-kappa B; D014763:Viral Matrix Proteins; D015847:Interleukin-4