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Translational study on the antigen presenting prop.. (BcellsMiceToMen)
Translational study on the antigen presenting properties of human vs mouse B cell subpopulations
(BcellsMiceToMen)
Date du début: 15 avr. 2010,
Date de fin: 14 avr. 2013
PROJET
TERMINÉ
Our recent results on antitumor effects of carbohydrate mimotope peptides (CMP) suggest a possible role of carbohydrate reactive B cell subpopulations as cellular adjuvants. As an abundant alternative of dendritic cells, CD40-activated B cells can efficiently present specific antigens being expandable for several weeks. Some B cells can be sufficiently detrimental to warrant anti-B cell therapy in cancer. Other (mouse) B cell subsets (e.g. B1 and marginal zone (MZ) B cells) seem as effective as mature DC, including skewing the T cell to the desirable Th1 responses. Thus, B subpopulations deserve scrutiny as the optimal antigen presenting cells. We hypothesize that CMP target carbohydrate reactive B cells, which present the collinear T cell epitopes to auxiliary T cells, create an environment conducive to epitope spreading to glycoprotein tumor antigens. The major mature B cell subpopualtions in the mouse are B2 follicular cells, MZ B cells, as well as B1a and B1b peritoneal B cells. The translation of a B cell strategy to the clinic is hindered by lack of straightforward functional homologies between mouse and human B cell subsets. Therefore, we propose to study the potential of ex vivo expanded human B cell subpopulations to present CMP and induce an appropriate cytokine environment for the development of anti-tumor CTL responses in comparison to the mouse system. To this end we propose to compare the phenotype and antigen presenting properties of mouse and human CMP specific B cells. These studies will allow for the design of therapeutic approaches based on ex vivo expansion of phenotypically similar B cells and using them for active immunotherapy of cancer after loading with appropriate antigens. The relevance of the CMP specific system to a bulk population of the same phenotype stems from the capacity of B cells to present antigens targeted nonspecifically for instance to CD19.
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