title: Presentation of the candidate rheumatoid arthritis autoantigen aggrecan by antigen-specific B cells induces enhanced CD4(+)  T helper type 1 subset differentiation.
abstract: Effective immune responses require antigen uptake by antigen-presenting cells (APC), followed by controlled endocytic proteolysis resulting in the generation of antigen-derived peptide fragments that associate with intracellular MHC class II molecules. The resultant peptide-MHC class II complexes then move to the APC surface where they activate CD4(+)  T cells. Dendritic cells (DC), macrophages and B cells act as efficient APC. In many settings, including the T helper type 1 (Th1) -dependent, proteoglycan-induced arthritis model of rheumatoid arthritis, accumulating evidence demonstrates that antigen presentation by B cells is required for optimal CD4(+)  T cell activation. The reasons behind this however, remain unclear. In this study we have compared the activation of CD4(+)  T cells specific for the proteoglycan aggrecan following antigen presentation by DC, macrophages and B cells. We show that aggrecan-specific B cells are equally efficient APC as DC and macrophages and use similar intracellular antigen-processing pathways. Importantly, we also show that antigen presentation by aggrecan-specific B cells to TCR transgenic CD4(+)  T cells results in enhanced CD4(+)  T cell interferon-γ production and Th1 effector sub-set differentiation compared with that seen with DC. We conclude that preferential CD4(+)  Th1 differentiation may define the requirement for B cell APC function in both proteoglycan-induced arthritis and rheumatoid arthritis.
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne, UK.
authors.forename: Caroline L
authors.initials: CL
authors.lastname: Wilson
authors.forename: Dominic W
authors.initials: DW
authors.lastname: Hine
authors.forename: Ariel
authors.initials: A
authors.lastname: Pradipta
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Pearson
authors.forename: Willem
authors.initials: W
authors.lastname: van Eden
authors.forename: John H
authors.initials: JH
authors.lastname: Robinson
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Knight
mesh_terms: D053674:Aggrecans / Q000737:chemistry / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism; D001324:Autoantigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology* / Q000276:immunology
chemical_list: D053674:Aggrecans; D001324:Autoantigens; D010455:Peptides