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Presentation of the candidate rheumatoid arthritis autoantigen aggrecan by antigen-specific B cells induces enhanced CD4+T helper type 1 subset differentiation

Lookup NU author(s): Dominic Hine, Ariel Pradipta, Professor Jeffrey Pearson, Professor John Robinson, Dr Andrew Knight

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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 peptideMHC 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-? 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.

Publication metadata

Author(s): Wilson CL, Hine DW, Pradipta A, Pearson JP, van Eden W, Robinson JH, Knight AM

Publication type: Article

Publication status: Published

Journal: Immunology

Year: 2012

Volume: 135

Issue: 4

Pages: 344-354

Print publication date: 02/03/2012

ISSN (print): 0019-2805

ISSN (electronic): 1365-2567

Publisher: Wiley-Blackwell Publishing Ltd.

URL: http://dx.doi.org/10.1111/j.1365-2567.2011.03548.x

DOI: 10.1111/j.1365-2567.2011.03548.x

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