B cell receptors and complement receptors target the antigen to distinct intracellular compartments.
The processing of exogenous Ags is an essential step for the generation of immunogenic peptides that will be presented to T cells. This processing relies on the efficient intracellular targeting of Ags, because it depends on the content of the compartments in which Ags are delivered in APCs. Opsonization of Ags by the complement component C3 strongly enhances their presentation by B cells and increases their immunogenicity in vivo. To investigate the role of C3 in the targeting of Ags, we compared the intracellular traffic of proteins internalized by complement receptor (CR) and B cell receptor (BCR) in B lymphocytes. Whereas both receptors are able to induce efficient Ag presentation, their intracellular pathways are different. CR ligand is delivered to compartments containing MHC class II molecules (MHC-II) but devoid of transferrin receptor and Lamp-2, whereas BCR rapidly targets its ligand toward Lamp-2-positive, late endosomal MHC-II-enriched compartments through intracellular vesicles containing transferrin receptor. CR and BCR are delivered to distinct endocytic pathways, and the kinetic evolution of the protein content of these pathways is very different. Both types of compartments contain MHC-II, but CR-targeted compartments receive less neosynthesized MHC-II than do BCR-targeted compartments. The targeting induced by CR toward compartments that are distinct from BCR-targeted compartments probably participates in C3 modulation of Ag presentation.
Laboratoire d'Immunochimie, Département de Réponse et Dynamique Cellulaires, Commissariat à l'Energie Atomique, Institut National de la Santé et de la Recherche Médicale, Unité 548, Université Joseph Fourier, Grenoble, France.
Laure A
LA
Perrin-Cocon
Christian L
CL
Villiers
Jean
J
Salamero
Françoise
F
Gabert
Patrice N
PN
Marche
D017951:Antigen Presentation; D000942:Antigens, Bacterial / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002461:Cell Line, Transformed; D003176:Complement C3 / Q000378:metabolism / Q000502:physiology; D003179:Complement C3b / Q000378:metabolism; D004705:Endocytosis / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D006801:Humans; D016056:Immunodominant Epitopes / Q000378:metabolism; D007424:Intracellular Fluid / Q000276:immunology* / Q000378:metabolism*; D008024:Ligands; D011485:Protein Binding / Q000276:immunology; D021381:Protein Transport / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism / Q000502:physiology*; D017463:Receptors, Complement 3b / Q000378:metabolism / Q000502:physiology*; D013744:Tetanus Toxin / Q000276:immunology / Q000378:metabolism; D022161:Transport Vesicles / Q000276:immunology
D000942:Antigens, Bacterial; D003176:Complement C3; D000949:Histocompatibility Antigens Class II; D016056:Immunodominant Epitopes; D008024:Ligands; D011947:Receptors, Antigen, B-Cell; D017463:Receptors, Complement 3b; D013744:Tetanus Toxin; D003179:Complement C3b