Trafficking of the Igα/Igβ heterodimer with membrane Ig and bound antigen to the major histocompatibility complex class II peptide-loading compartment

The binding of antigen to the B cell antigen receptor (BCR) initiates two major cellular events. First, upon cross linking by antigen, the BCR induces signal transduction cascades leading to the transcription of a number of genes associated with B cell activation. Second, the BCR internalizes and delivers antigens to processing compartments, where processed antigenic peptides are loaded onto major histocompatibility complex (MHC) class II molecules for presentation to T helper cells. The BCR consists of membrane Ig (mIg) and Ig alpha/ Ig beta heterodimer (Ig alpha/Ig beta). The Ig alpha/Ig beta, the signal transducing component of the BCR, has been indicated to play a role in antigen processing. In order to understand the function of the Ig alpha/Ig beta in antigen transport, we studied the intracellular trafficking pathway of the Ig alpha/Ig beta. We show that in the absence of antigen binding, the Ig alpha/Ig beta constitutively traffics with mig from the plasma membrane, through the early endosomes, to the MHC class II peptide-loading compartment. Cross-linking the BCR does not alter the trafficking pathway; however, it accelerates the transport of the Ig alpha/Ig beta to the MHC class II peptide-loading compartment. This suggests that the Ig alpha/Ig beta heterodimer is involved in BCR-mediated antigen transport through the entire antigen transport pathway.