Endocytosed BCRs sequentially regulate MAPK and Akt signaling pathways from intracellular compartments.

Binding of antigen to the B cell antigen receptor (BCR) triggers both BCR signaling and endocytosis. How endocytosis regulates BCR signaling remains unknown. Here we report that BCR signaling was not extinguished by endocytosis of BCRs; instead, BCR signaling initiated at the plasma membrane continued as the BCR trafficked intracellularly with the sequential phosphorylation of kinases.