Figure 1.

Regulation of B cell differentiation and functions by intracellular membranes and associated proteins. Several B cell processes are regulated by endosomes, lysosomes, and autophagosomes. Upon antigen-triggered internalization, BCR is sorted by early endosomes to either recycle back onto the cell surface or go through antigen processing, which are mediated by endolysosomes, for the MHC II-dependent antigen presentation. Signaling receptors, such as CD40 (as depicted) and TLRs (both surface TLRs and intracellular TLRs), can be internalized and/or sorted by early endosomes to localize to mature late endosomes, as marked by Rab7. A Rab7-dependent process would stabilize the interaction of such receptors and their adaptors (e.g., CD40 and TRAF6), thereby promoting sustained signaling, such as NF-κB activation, for induction of genes important for B cell activation and CSR/SHM, e.g., AID. Lysosomes, as transformed from and maintained by mature late endosomes, can recruit mTOR, which plays an important role in B cell activation. Autophagosomes are important for memory B cell maintenance, i.e., through Atg7, and plasma cell differentiation and survival, e.g., through Atg5. They can also fuse with lysosomes to become autolysosomes, which then transform into a specialized compartment for antigen presentation.