SELECTIVE MODULATION OF THE MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-IIANTIGEN PRESENTATION PATHWAY FOLLOWING B-CELL RECEPTOR LIGATION AND PROTEIN-KINASE-C ACTIVATION

We noticed that B cell receptor ligation or phorbol 12-myristate 13-ac etate treatment induced intracellular vesicles containing major histoc ompatibility complex (MHC) class II and invariant chain (Ii), and incr eased the amount of transmembrane p12 Ii fragments coimmunoprecipitate d with class II molecules. To determine the influence of protein kinas e C activation on the MHC class II presentation pathway, we analyzed t he subcellular distribution of Ii, the induction of SDS-stable forms o f class II molecules, and their ability to present different antigens. Ii chains visualized with luminal and cytoplasmic directed antibodies appeared in early endosomal compartments accessible to transferrin in response to phorbol 12-myristate 13-acetate treatment, whereas transm embrane Ii degradation products equivalent to the p12 Ii fragments wer e colocalized with the B cell receptors internalized after cross-linki ng. Protein kinase C activation delayed in parallel the formation of S DS-stable forms of class II molecules and reduced the presentation of antigenic determinants requiring newly synthesized class II alpha beta -Ii complexes. These data indicate that B cell activation affects Ii p rocessing and MHC class II peptide loading in endosomal compartments i ntersecting the biosynthetic pathway.