Background Zeta-chain-associated protein kinase 70 (ZAP-70), a tyrosine kinase constitutively expressed in T cells, can be found in B cells and is used as a prognostic marker in identifying different forms of chronic lymphocytic leukemia. We previously provided evidence that a subset of B cells in patients with rheumatoid arthritis (RA) expresses ZAP-70, that marks the memory B cell subsets (IgD+CD27+ and IgD-CD27+), thus suggesting that the ZAP-70+ B cells represent a memory activated subset likely involved in the maintenance of an activated B cell pool [1–3].
Objectives The aim of the present study was to clarify whether B cells, especially ZAP-70 expressing B cells, represent indeed a risk for a severe expression of arthritis in a transgenic ZAP-70+B murine model.
Methods Male transgenic ZAP-70+B mice, that has already been shown to present an high ZAP-70 expression in the B cell lineage , aged 8–12 weeks old were used for experiments. All the animals were injected with a cocktail of 5 monoclonal antibodies recognizing the conserved epitopes on various species of type II collagen. Three days later the mice were injected with LPS from E. coli 0111:B4 to trigger arthritis development. Animals were evaluated every 3 days after the infusion of the antibody cocktail for arthritis incidence and each paw was evaluated and scored individually on a scale of 0–4. An arthritis index (AI) that expressed a cumulative score for all paws was calculated for each animal.
Results We found that the transgenic ZAP-70+B cells mice presented a more severe form of arthritis, compared to wild type age-matched mice (p<0.001) (Figure). Histological and immunohistochemical analyses confirmed the presence of joint erosions and inflammatory infiltrate at the level of the synovium of ZAP-70+B cells mice.
Conclusions These data suggest that B cells amplify the degree of CAIA, that ZAP-70 is involved in the pathogenesis of arthritis in an RA-like model, and that this tyrosine kinase likely represents a possible target of therapy.
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Disclosure of Interest None declared