Dendritic cells genetically modified to express CD40 ligand and pulsed with antigen can initiate antigen-specific humoral immunity independent of CD4+ T cells.
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.
Kikuchi
T
T
Division of Pulmonary and Critical Care Medicine of the Department of Medicine, Weill Medical College of Cornell University, New York, New York, USA.
Worgall
S
S
Singh
R
R
Moore
M A
MA
Crystal
R G
RG
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
D016207:Cytokines; D023201:CD40 Ligand