title: The pathway of antigen uptake and processing dictates MHC class II-mediated B cell survival and activation.
abstract: The influence of the pathway of Ag uptake and processing on MHC class II (CII)-mediated B cell function is unknown. In this study, we investigate in resting and activated (via the BCR or CD40) B cells the biological properties of CII-peptide complexes (CII-peptide) generated by either the BCR-mediated Ag processing (type I complex) or fluid phase Ag processing (type II complex). Compared with type I complex, ligation of type II complex by either specific Ab or the TCR in Ag-presenting assay results in significant decreases in B cell survival rate (50-100%) and expression levels of CII, CD86, and CD54. Loss of B cells following ligation of type II complex occurs in the presence of a comparatively good level of specific CD4(+) T cell division, indicating that B cell loss is a late event following T cell stimulation. Comparative analysis of T and B cell conjugates after Ab ligation of type I or II complex reveals decreased efficiency of the latter in forming conjugates. Neither initial differential levels of CII and other studied surface markers, B cell type inherent differences, BCR signaling, T cell proliferation, nor initial density of CII-peptide complexes could explain the T cell-induced B cell loss. We propose that the context in which CII-peptide complexes are present in the membrane following BCR uptake and processing leads to B cell survival. Thus, appropriate targeting of Ag ensures generation of relevant immune responses.
authors.affiliation: Albany Medical College, Center for Immunology and Microbial Disease, Albany, NY 12208, USA.
authors.forename: Toufic O
authors.initials: TO
authors.lastname: Nashar
authors.forename: James R
authors.initials: JR
authors.lastname: Drake
mesh_terms: D000818:Animals; D000906:Antibodies / Q000378:metabolism; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology*; D000941:Antigens / Q000276:immunology / Q000378:metabolism*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D001666:Binding Sites, Antibody; D002450:Cell Communication / Q000276:immunology; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D004261:DNA Replication / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D007700:Kinetics; D008024:Ligands; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009113:Muramidase / Q000276:immunology* / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D014176:Protein Biosynthesis / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
chemical_list: D000906:Antibodies; D000941:Antigens; D000944:Antigens, Differentiation, B-Lymphocyte; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D008024:Ligands; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; C421864:hen egg lysozyme; D009113:Muramidase