Major histocompatibility complex class II-independent generation of neutralizing antibodies against T-cell-dependent Borrelia burgdorferi antigens presented by dendritic cells: Regulation by NK and gamma delta T cells

We previously showed that adoptive transfer of Borrelia burgdorferi-pulsed dendritic cells (DCs) into syngeneic mice protects animals from challenge w ith tick-transmitted spirochetes, Here, we demonstrate that the protective immune response is antibody (Ab) dependent and does not require the presenc e of major histocompatibility complex (MHC) class II molecules on DCs. Mice sensitized with B. burgdorferi-pulsed MHC class II-deficient (MHC class II -/-) DCs mounted a humoral response against protective antigens, including B. burgdorferi outer surface protein A (OspA) and OspC, B-cell help for the generation of neutralizing anti-OspC immunoglobulin G Abs could be provide d by gamma delta T cells. In contrast, anti-OspA Ab production required the presence of alpha beta T cells, although this pathway could be independent of MHC class II molecules on antigen-presenting cells. Moreover, depletion of NK cells prior to transfer of antigen-pulsed MHC class II-/- DCs result ed in significant increases in the levels of neutralizing Abs induced by DC s, Altogether, these data suggest that the initial interactions between DCs and innate immune cells, such as gamma delta and NK cells, can influence t he generation of a protective humoral response against B, burgdorferi antig ens.