title: Dendritic cells genetically modified to express CD40 ligand and pulsed with antigen can initiate antigen-specific humoral immunity independent of CD4+ T cells.
abstract: We have investigated whether dendritic cells genetically modified to express CD40 ligand and pulsed with antigen can trigger B cells to produce antigen-specific antibodies without CD4+ T-cell help. Dendritic cells modified with a recombinant adenovirus vector to express CD40 ligand and pulsed with heat-killed Pseudomonas induced naive B cells to produce antibodies against Pseudomonas in the absence of CD4+ T cells in vitro, initiated Pseudomonas-specific humoral immune responses in vivo in wild-type and CD4-/- mice, and protected immunized wild-type and CD4-/-, but not B-cell -/- mice, from lethal intrapulmonary challenge with Pseudomonas. Thus, genetic modification of dendritic cells with CD40 ligand enables them to present a complex mixture of microbial antigens and establish CD4+ T cell-independent, B cell-mediated protective immunity against a specific microbe.
authors.affiliation: Division of Pulmonary and Critical Care Medicine of the Department of Medicine, Weill Medical College of Cornell University, New York, New York, USA.
authors.forename: T
authors.initials: T
authors.lastname: Kikuchi
authors.forename: S
authors.initials: S
authors.lastname: Worgall
authors.forename: R
authors.initials: R
authors.lastname: Singh
authors.forename: M A
authors.initials: MA
authors.lastname: Moore
authors.forename: R G
authors.initials: RG
authors.lastname: Crystal
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D023201:CD40 Ligand / Q000235:genetics* / Q000378:metabolism; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000502:physiology*; D005260:Female; D005818:Genetic Engineering / Q000379:methods; D005822:Genetic Vectors; D007114:Immunization / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D011552:Pseudomonas Infections / Q000276:immunology / Q000517:prevention & control; D011550:Pseudomonas aeruginosa / Q000276:immunology
chemical_list: D016207:Cytokines; D023201:CD40 Ligand