Prolonged antigen persistence within nonterminal late endocytic compartments of antigen-specific B lymphocytes

Although Ag-specific B lymphocytes can process Ag and express peptide-class II complexes as little as 1 h after Ag exposure, it requires 3-5 days for the immune system to develop a population of Ag-specific effector CD4 T lymphocytes to interact with these complexes. Presently, it is unclear how B cells maintain the expression of cell surface antigenic peptide-class II complexes until effector CD4 T lymphocytes become available. Therefore, we investigated B cell receptor (BCR)-mediated Ag processing and presentation by normal B lymphocytes to determine whether these cells have a mechanism to prolong the cell surface expression of peptide-class II complexes derived from the processing of cognate AG: Interestingly, after transit of early endocytic compartments, internalized Ag-BCR complexes are delivered to nonterminal late endosomes where they persist for a prolonged period of time. In contrast, Ags internalized via fluid phase endocytosis are rapidly delivered to terminal lysosomes and degraded. Moreover, persisting Ag-BCR complexes within nonterminal late endosomes exhibit a higher degree of colocalization with the class II chaperone HLA-DM/H2-M than with the HLA-DM/H2-M regulator HLA-DO/H2-O. Finally, B cells harboring persistent Ag-BCR complexes exhibit prolonged cell surface expression of antigenic peptide-class II complexes. These results demonstrate that B lymphocytes possess a mechanism for prolonging the intracellular persistence of Ag-BCR complexes within nonterminal late endosomes and suggest that this intracellular Ag persistence allows for the prolonged cell surface expression of peptide-class II complexes derived from the processing of specific AG: