SorLA regulates B cell receptor uptake, trafficking, and B cell-mediated immune responses in vivo

A high-affinity antibody response to both infection and vaccination critically relies on the ability of B cells to capture and process antigen for presentation to CD4+ T cells. The cellular processes from antigen recognition to full B cell activation require a finely orchestrated series of events, involving signalling and intracellular trafficking mechanisms. Here, we describe a novel regulator of B cell receptor (BCR) endocytosis and intracellular trafficking. Multidomain trafficking protein sorting-related receptor with A-type repeats (SorLA) associates with the BCR and regulates uptake of both soluble and substrate-bound antigens. SorLA deletion results in altered BCR-antigen intracellular trafficking to degradative compartments, modulating eventual antigen presentation. Crucially, this change in antigen trafficking results in a significant reduction in plasma cells and humoral responses in vivo. Given the critical importance of antigen presentation in immunity, as well as autoimmune disease and malignancy, these results identify a new cellular pathway in B cell biology with potential implications for immune regulation.