The immunobiology of ubiquitin-dependent B cell receptor functions

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HighlightsThe B cell receptor (BCR) mediates the processing and presentation of cognate foreign antigen.Ubiquitination of the BCR controls its trafficking to and within intracellular antigen processing compartments.BCR-mediated antigen processing results in formation of peptide-class II complexes with unique biological/immunological properties.MHC class II-restricted antigen presentation by dendritic cells is necessary for activation of naïve CD4 T cells, whereas class II-restricted antigen presentation by B lymphocytes and macrophages is important for the recruitment of CD4+ helper and regulatory T cells. Antigen presentation by B cells is also important for induction of T cell tolerance. B cells are unique among these three types of MHC class II-expressing antigen presenting cells (APC) as they constitutively express high levels of cell surface class II molecules and express a clonally restricted antigen specific receptor, the B cell receptor (BCR). Here, I review our current understanding of three major steps that underlie the processing and presentation of BCR-bound cognate antigen: (1) endocytosis of antigen-BCR (Ag-BCR) complexes, (2) Ag-BCR trafficking to intracellular antigen processing compartments and (3) generation of antigenic peptide-MHC class II complexes, with a particular focus on the role of BCR ubiquitination in each. I will highlight potential topics for future research and briefly discuss the impact of the cell biology of BCR-mediated antigen processing on the response of the B cell and T cell to the cell-cell interactions mediated by B cell-expressed peptide-class II complexes.

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