title: T cell independent secondary antibody responses to the envelope protein of simian immunodeficiency virus.
abstract: BACKGROUND
  During human (HIV) and simian (SIV) immunodeficiency virus infection, loss of CD4+ T cells and progression to AIDS are associated with a decline in antibody titers to the viral Gag protein, while antibodies to the Env protein remain high, suggesting a T cell independent antibody response to Env.
  
  
  RESULTS
  To explore differential regulation of Gag and Env antibody responses, immunocompetent BALB/c and T cell deficient nude mice were immunized with virus like particles (VLP) of simian immunodeficiency virus or adenoviral vectors expressing SIV Gag and Env. High levels of antibodies against Gag and Env could only be induced in immunocompetent mice, but not in the immunodeficient mice. Thus, neither cells expressing Env after adenoviral gene transfer nor VLPs induce a T cell independent primary anti-Env antibody response. However, secondary B cell responses to Env, but not to Gag, were observed in immunodeficient mice after transfer of primed B cells and boosting with VLPs or adenoviral vectors expressing Gag and Env. This T cell independent secondary antibody response to Env was reduced after stimulation with VLPs modified to contain monomeric membrane bound gp130 surface subunit of Env and undetectable after injection of soluble gp130.
  
  
  CONCLUSIONS
  Membrane-bound trimeric Env seems to be responsible for the maintenance of high levels of anti-Env antibodies during progression to AIDS. This T cell independent secondary antibody response may prevent T cell-dependent affinity maturation and thus contribute to viral immune escape by favoring persistence of non-protective antibodies.
authors.affiliation: Department of Molecular and Medical Virology, Ruhr University Bochum, D-44780, Bochum, Germany.
authors.forename: Ghulam
authors.initials: G
authors.lastname: Nabi
authors.forename: Vladimir
authors.initials: V
authors.lastname: Temchura
authors.forename: Claudius
authors.initials: C
authors.lastname: Grossmann
authors.forename: Seraphin
authors.initials: S
authors.lastname: Kuate
authors.forename: Matthias
authors.initials: M
authors.lastname: Tenbusch
authors.forename: Klaus
authors.initials: K
authors.lastname: Überla
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000821:virology; D000256:Adenoviridae; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002462:Cell Membrane / Q000378:metabolism; D018450:Disease Progression; D015683:Gene Products, gag / Q000276:immunology; D005822:Genetic Vectors; D057131:Immune Evasion; D007117:Immunization, Secondary; D016867:Immunocompromised Host; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D015302:Simian Immunodeficiency Virus / Q000276:immunology* / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000276:immunology* / Q000378:metabolism
chemical_list: D000914:Antibodies, Viral; D015683:Gene Products, gag; D014759:Viral Envelope Proteins