Cell surface recycling of internalized antigen permits dendritic cell priming of B cells.
Dendritic cells process internalized antigens to present degradative products on MHC for TCR recognition. Because antigen-exposed DCs also induce humoral immunity, DCs must also retain antigen in its native state for the engagement of BCR on B cells. Here, we demonstrate that antigen endocytosed by the inhibitory Fc receptor, FcgammaRIIB, accesses a non-degradative intracellular vesicular compartment that recycles to the cell surface, enabling interaction of native antigen with BCR on B cells. Immunization with IgG-opsonized, T independent antigens leads to enhanced humoral responses in a FcgammaRIIB and complement dependent manner. IC-loaded DCs trafficking to the splenic marginal zone can prime a T independent response in an FcgammaRIIB-dependent manner. Thus dendritic cells are equipped with both non-degradative and degradative antigen uptake pathways to facilitate antigen presentation to both B and T cells.
Bergtold
Amy
A
Integrated Program in Cellular, Molecular, and Biophysical Studies, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
Desai
Dharmesh D
DD
Gavhane
Anamika
A
Clynes
Raphael
R
D000818:Animals; D017951:Antigen Presentation; D000941:Antigens / Q000276:immunology* / Q000378:metabolism*; D015703:Antigens, CD / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D004705:Endocytosis; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D017452:Receptors, IgG / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D000941:Antigens; D015703:Antigens, CD; C080571:Fc gamma receptor IIB; D017452:Receptors, IgG