Abstract
Abstract Upon recognition of specific antigens, B cells commit to receptor-mediated endocytosis and subsequent processing of antigen into peptides for presentation on MHC class II (MHCII) molecules. This highly specific and efficient antigen presentation is a prerequisite for B cells to be able to receive T cell help and initiate high-affinity antibody responses. The intracellular vesicle trafficking and the identity of the compartments vital for antigen processing and peptide-MHCII presentation remain poorly known. We set to characterize the vesicular pathway of internalized antigen in B cells via extensive co-localization analysis using various different markers. Our data reveal involvement of both classical endosomal markers and more specialized vesicular regulators. It appears that B cells process antigen in atypical endosomes that share both early (EEA1+, Rab5+) and late (Rab7+, Rab9+, LAMP1+) endosomal markers together with Cathepsin-S, required for proteolytic processing. Interestingly, a small GTPase Rab8, linked to specialized protein secretion pathways in the literature, strongly colocalizes with antigen throughout different stages of vesicle transport. To investigate the functional role of Rab8 on B cell antigen processing, we went on to generate Rab8-deficient B cell lines by CRISPR/Cas9. Notably, we detected a dramatic loss of antigen presentation in the cells deficient in Rab8. Our preliminary data points towards a role for Rab8 both in the transport of antigen as well as MHCII.
Published Version
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