Figure 1.

Molecular mechanisms of BCR internalization. Clathrin-mediated endocytosis (green). Following BCR antigen binding, clathrin is recruited to BCR-antigen clusters, binding ITAM residues in the cytoplasmic tails of Igα and Igβ. Clathrin polymerization induces membrane-curvature and formation of CCPs. CCPs invaginate before scission from the PM mediated by dynamin, forming a CCV. CCVs containing BCR-antigen complexes fuse with late endosomes for antigen processing and subsequent presentation. Phagocytosis (blue). BCR binding to large, particulate antigens can induce local actin rearrangements, driving membrane protrusion to form a large membrane invagination. Once internalized in phagosomes, the membrane vesicle undergoes fusion events in parallel with other endocytic processes. Fast endophilin-mediated endocytosis (yellow). Within endophilin-primed membrane patches, BCR antigen binding results in endophilin-mediated membrane curvature with subsequent dynamin scission to form an intracellular vesicle. This pathway is specific for ligand-triggered, signaling receptors. Caveolin-dependent endocytosis (pink). Caveolin-1 controls the distribution of surface BCR into lipid rafts. Its role in antigen-mediated BCR internalization requires further investigation. Created with BioRender.com.