CD1d mediated ganglioside presentation by human B cells: novel pathway to recruit NKT cells’ help

FAINBOIM, L; FASSA, S.; ARANA, E.; SOMAGLIA, V.; PEREZ, M.E.

Buenos Aires

Congreso; First French-Argentine Immunology Congress y LVIII Reunión Anual de la Sociedad Argentina de Inmunología; 2010

Sociedad Argentina de Inmunología

Gangliosides are a family of sialylated glycolipids that are normal components of the cell membrane(1). Being a ganglioside itself, N-glycolyl-GM3 (NGcGM3) is not expressed in normal human tissues though, owing to a specie-specific genetic mutation that abrogates its biosynthesis. However, it is highly expressed in tumours. As a result, it has been a target of choice for immunotherapy, and it has been proved an antibody response against NGcGM3(2). B lymphocytes produce antibodies upon antigen (Ag) induced activation and are capable of presenting internalized Ags(3). This is well established for peptide Ags, yet antibody response against glicolipids remains poorly characterized. Notably, a compartment of T cells, known as natural killer T (NKT), recognize and become activated in response to glycolipid Ags presented by CD1d molecules expressed on the surface of antigen presenting cells(4). In this study, we aimed to assess whether B cells were competent to present NGcGM3 to NKT. To achieve so, we isolated lymphocytes from human sources, sorted the populations of interest and co-cultured them with NGcGM3. By flow cytometry techniques, we show that primary human B cells express CD1d, in resting and activated state. Importantly, we demonstrate that human B cells are capable of presenting NGcGM3 via these CD1d molecules. Upon setting up an assay of isolation and expansion of human NKTs from buffy coats, we prove an enhancement of their proliferation in co-cultures with autolog NGcGM3-loaded B lymphocytes in relation to single cultures. Taken together, these findings not only aid to establish principles in relation to the mechanism of the humoral response to gangliosides, but also potentially to improve tumor vaccinations´ strategies.