Measles virus nucleocapsid protein binds to FcgammaRII and inhibits human B cell antibody production.
Despite the development of an efficient specific immune response during measles virus (MV) infection, an immunosuppression occurs contributing to secondary infections. To study the role of nucleocapsid protein (NP) in MV-induced immunosuppression, we produced recombinant MV NP. Purified recombinant NP exhibited biochemical, antigenic, and tridimensional structure similar to viral NP. By flow cytometry, we showed that viral or recombinant NP bound to human and murine B lymphocytes, but not to T lymphocytes. This binding was specific, independent of MHC class II expression, and dependent of the B lymphocyte activation state. The murine IIA1. 6 B cell line, deficient in the Fc receptor for IgG (FcgammaRII) expression, did not bind NP efficiently. Transfected IIA1.6 cells expressing either murine FcgammaRIIb1 or b2, or human FcgammaRIIa, b1*, or b2 isoforms efficiently bound NP. Furthermore, this binding was inhibited up to 90% by monoclonal antibodies 2.4G2 or KB61 specific for murine and human FcgammaRII, respectively. Finally, the in vitro Ig synthesis of CD40- or Ig-activated human B lymphocytes in the presence of interleukin (IL)-2 and IL-10 was reduced by 50% in the presence of recombinant NP. These data demonstrate that MV NP binds to human and murine FcgammaRII and inhibits in vitro antibody production, and therefore suggests a role for NP in MV-induced immunosuppression.
Ravanel
K
K
Immunobiologie Moléculaire, Unité Mixte de Recherche 49, Centre National de la Recherche Scientifique-Ecole Normale Supérieure Lyon, 69364 Lyon Cedex 07, France.
Castelle
C
C
Defrance
T
T
Wild
T F
TF
Charron
D
D
Lotteau
V
V
Rabourdin-Combe
C
C
D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000502:physiology*; D002478:Cells, Cultured; D006801:Humans; D007108:Immune Tolerance; D008457:Measles / Q000276:immunology; D051379:Mice; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000502:physiology*; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D017452:Receptors, IgG / Q000502:physiology*; D014764:Viral Proteins / Q000502:physiology*
D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D011947:Receptors, Antigen, B-Cell; D017452:Receptors, IgG; D014764:Viral Proteins; C058314:nucleoprotein, Measles virus