Modeling the presentation of C3d-coated antigen by B lymphocytes: enhancement by CR1/2-BCR co-ligation is selective for the co-ligating antigen.
We have used a set of single-chain variable fragment antibodies (sc) genetically fused with an influenza hemagglutinin-derived peptide as a means to investigate the role of CR1 and CR2 in antigen presentation by B cells. When incubated with the B cell lymphoma 2PK3, peptide-containing sc specific for either CR1 or CR1/2 mediated activation of the hemagglutinin peptide-specific T cell line IP-12-7, as assessed by IL-2 production. Efficient presentation was dependent on the binding of the constructs to CR1/2, implying that receptor-mediated endocytosis is responsible for the effect. Cross-linkage of CR1/2 or CD19 by mAb did not increase the extent of T cell activation. However, when CR1/2 was co-ligated with the BCR--using either polyclonal goat anti-mouse IgG or recombinant protein LA--the antigen concentration required to activate T cells decreased by two orders of magnitude. Moreover, this enhancement was selective for the antigen included in these complexes and did not affect the presentation of a free peptide or of antigen bound to CR1/2 excluded from the complexes. These results suggest that B cells may bind various C3d-coated antigens at a time, but only the one which reacts with the BCR will be processed with high efficiency. This mechanism may ensure the specificity of cognate T cell help.
Prechl
József
J
Department of Immunology, Loránd Eötvös University, Pázmány Péter s. 1/C, Budapest, Hungary.
Baiu
Dana C
DC
Horváth
Attila
A
Erdei
Anna
A
D000818:Animals; D017951:Antigen Presentation; D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D015933:Complement C3d / Q000378:metabolism*; D051379:Mice; D018448:Models, Immunological; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D011951:Receptors, Complement / Q000502:physiology*; D017463:Receptors, Complement 3b / Q000502:physiology; D017464:Receptors, Complement 3d / Q000502:physiology; D014407:Tumor Cells, Cultured
D011947:Receptors, Antigen, B-Cell; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D017464:Receptors, Complement 3d; D015933:Complement C3d