MHC class II antigen processing in B cells: Accelerated intracellular targeting of antigens

Processing and presentation by Ag-specific B cells is initiated by Ag bindi ng to the B cell Ag receptor (BCR). Cross-linking of the BCR by Ag results in a rapid targeting of the BCR and bound Ag to the MHC class II peptide lo ading compartment (IIPLC). This accelerated delivery of Ag may be essential in vivo during periods of rapid Ag-driven B cell expansion and T cell-depe ndent selection. Here, we use both immunoelectron microscopy and a nondisru ptive protein chemical polymerization method to define the intracellular pa thway of the targeting of Ags by the BCR. We show that following cross-link ing, the BCR is rapidly transported through transferrin receptor-containing early endosomes to a LAMP-1(+), beta-hexosaminadase(+), multivesicular com partment that is an active site of peptide-class II complex assembly, conta ining both class II-invariant chain complexes in the process of invariant c hain proteolytic removal as well as mature peptide-class II complexes, The ECR enters the class II-containing compartment as an intact mLg/Ig alpha/Ig beta complex bound to Ag, The pathway by which the BCR targets Ag to the I IPLC appears not to be identical to that by which Ags taken up by fluid pha se pinocytosis traffick, suggesting that the accelerated BCR pathway may be specialized and potentially independently regulated.