Presentation of antigens internalized through the B cell receptor requiresnewly synthesized MHC class II molecules

Exogenous Ags taken up from the fluid phase ran he presented by both newly synthesized and recycling MHC class II molecules, However, the presentation of Ags internalized through the B cell receptor (BCR) has not been charact erized with respect to whether the class II molecules with which they becom e associated are newly synthesized or recycling. We show that the presentat ion of Ag taken up by the BCR requires protein synthesis in splenic a cells and in B lymphoma cells. Using B tells transfected with full-length I-A(k) molecules or molecules truncated in cytoplasmic domains of their alpha- or beta-chains, we further show that when an Ag is internalized by the BCR, t he cytoplasmic tails of class II molecules differentially control the prese ntation of antigenic peptides to specific T cells depending upon the import ance of proteolytic processing in the production of that peptide, Integrity of the cytoplasmic tail of the I-A(k) beta-chain is required for the prese ntation of the hen egg lysozyme determinant (46-61) following BCR internali zation, but that dependence is not seen for the (34-45) determinant derived from the same protein. The tail of the beta-chain is also of importance fo r the dissociation of invariant chain fragments from class II molecules, Ou r results demonstrate that Ags internalized through the BCR are targeted to compartments containing newly synthesized class II molecules and that the tails of class II beta-chains control the loading of determinants produced after extensive Ag processing.