Summary 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.
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