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:
Gondré-Lewis
T A
TA
Trudeau Institute, 100 Algonquin Avenue, Saranac Lake, NY 12983.
Moquin
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AE
Drake
J R
JR
D000818:Animals; D000941:Antigens / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002451:Cell Compartmentation / Q000276:immunology; D002460:Cell Line; D004705:Endocytosis / Q000276:immunology*; D018985:Epitopes, B-Lymphocyte / Q000378:metabolism*; D006681:HLA-D Antigens / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D007424:Intracellular Fluid / Q000276:immunology / Q000378:metabolism; D007700:Kinetics; D046911:Macromolecular Substances; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009113:Muramidase / Q000276:immunology* / Q000378:metabolism*; D010446:Peptide Fragments / Q000096:biosynthesis / Q000276:immunology; D021381:Protein Transport / Q000276:immunology; D013347:Subcellular Fractions / Q000276:immunology / Q000378:metabolism
D000941:Antigens; D018985:Epitopes, B-Lymphocyte; C416186:H-2O antigen; C416189:H2-M antigens; D006681:HLA-D Antigens; C084245:HLA-DM antigens; C046148:HLA-DO antigens; D000949:Histocompatibility Antigens Class II; D046911:Macromolecular Substances; D010446:Peptide Fragments; C421864:hen egg lysozyme; D009113:Muramidase