Protection against collagen‐induced arthritis in mice afforded by the parasitic worm product,ES‐62, is associated with restoration of the levels of interleukin‐10‐producing B cells and reduced plasma cell infiltration of the joints

We have previously reported that ES‐62, a molecule secreted by the parasitic filarial nematode Acanthocheilonema viteae, protects mice from developing collagen‐induced arthritis (CIA). Together with increasing evidence that worm infection may protect against autoimmune conditions, this raises the possibility that ES‐62 may have therapeutic potential in rheumatoid arthritis and hence, it is important to fully understand its mechanism of action. To this end, we have established to date that ES‐62 protection in CIA is associated with suppressed T helper type 1 (Th1)/Th17 responses, reduced collagen‐specific IgG2a antibodies and increased interleukin‐10 (IL‐10) production by splenocytes. IL‐10‐producing regulatory B cells have been proposed to suppress pathogenic Th1/Th17 responses in CIA: interestingly therefore, although the levels of IL‐10‐producing B cells were decreased in the spleens of mice with CIA, ES‐62 was found to restore these to the levels found in naive mice. In addition, exposure to ES‐62 decreased effector B‐cell, particularly plasma cell, infiltration of the joints, and such infiltrating B cells showed dramatically reduced levels of Toll‐like receptor 4 and the activation markers, CD80 and CD86. Collectively, this induction of hyporesponsiveness of effector B‐cell responses, in the context of the resetting of the levels of IL‐10‐producing B cells, is suggestive of a modulation of the balance between effector and regulatory B‐cell responses that may contribute to ES‐62‐mediated suppression of CIA‐associated inflammation and inhibition of production of pathogenic collagen‐specific IgG2a antibodies.