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 expres s CD40 ligand and pulsed with antigen can trigger B cells to produce antige n-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 agains t Pseudomonas in the absence of CD4(+) T cells in vitro, initiated Pseudomo nas-specific humoral immune responses in vivo in wild-type and CD4(-/-) mic e, and protected immunized wild-type and CD4(-/-), but not B-cell(-/-) mice , from lethal intrapulmonary challenge with Pseudomonas. Thus, genetic modi fication of dendritic cells with CD40 ligand enables them to present a comp lex mixture of microbial antigens and establish CD4(+) T cell-independent, B cell-mediated protective immunity against a specific microbe.