Role of exosomes in B cell development and antibodies class switching recombination

Abstract

Exosomes are nanoparticles being released by various types of cells and they often carry functional cargo, including RNA and proteins, and provide a means to shuttle these cargos between cells. Emerging evidence suggest that exosomes are vital player in process such as intercellular communication and indirect gene regulation through protein and non-coding RNA cargo. The ability of efficient and secure exosome-mediated molecules transfers leads to a novel avenue to understand immune response regulation towards diseases and cancers. Several research groups have proven that exosomes are involved in intercellular communication between dendritic cells, T cells and B cells. Nonetheless, B-to-B cell communication and regulation of adaptive immune response via exosomal pathway haven’t been well studied. In this thesis, we investigated the role of exosomes in B cell development and antibody class switching recombination (CSR), an important process in adaptive immune response where mature B cells respond to antigens and secret classes of antibodies in order to diversify antibodies’ effector function. We observed CSR impairment under the depletion of bovine exosomes in cell medium and endogenous exosomes derived from CH12, a murine B lymphoma cell line.. Interestingly, complement of exosomes from naïve CH12 appear to be suppressive for CSR whilst exosomes from activated CH12 show a facilitating effect. Preliminary investigation in exosomal RNA showed selective packaging of exosomal cargo during CSR and such findings could provide a more accurate direction in understanding exosome-mediated regulation in CSR.