W160 - il-10-producing Dendritic Cells Modulate B Cell Responses

Juulke Steuten – Department of Immunopathology – Sanquin Research and Landsteiner Laboratory; Anja Ten Brinke – Department of Immunopathology – Sanquin Research and Landsteiner Laboratory; Marieke van Ham – Department of Immunopathology – Sanquin Research and Landsteiner Laboratory, Swammerdam Institute for Life Sciences, University of Amsterdam; Silvia Gregori – 1San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), Milan, Italy

Abstract Text: Tolerogenic dendritic cells (tolDC) play a critical role in promoting antigen(Ag)-specific tolerance. We developed a method to efficiently generate tolDC by genetic engineering of monocytes with lentiviral vectors encoding for human IL-10 (DCIL-10). DCIL-10 secrete supra-physiological levels of IL-10, modulate CD4 and CD8 T cell responses and promote allo-specific Type-1-regulatory T (Tr1) cells in vitro and in vivo. Since IL-10 has been shown to modulate B cell responses, we aimed at defining whether DCIL-10 modulate B cell responses in vitro in terms of activation and maturation in T-cell independent and dependent manner. Results revealed that proliferation, percentage of antibody-secreting cells and isotype switching were increased in naïve and memory B cells activated in the presence of DCIL-10. In memory B cells activation in the presence of DCIL-10 significantly decreased the IgG membrane expression, while increasing the IgG secretion. DCIL-10-mediated modulation of naïve B cell occurred in cell-to-cell contact, while modulation of memory B cells is IL-10 dependent. Memory B cells stimulated with DCIL-10 are less effective than those stimulated with control DC to promote allogeneic T cells activation. Finally, DCIL-10 promotes survival without modulating phenotype and isotype switching when naïve and memory B cells were activated in a T-cell dependent manner.
In conclusion, for the first time we report that tolerogenic IL-10-producing DC directly modulate B cells in vitro. In vivo investigations are ongoing to better define the impact of DCIL-10 on B cell responses in vivo.