A filarial nematode secreted product differentially modulates expression and activation of protein kinase C isoforms in B lymphocytes

Filarial nematodes, parasitic worms that cause elephantiasis, chronic skin lesions, and blindness in the tropics, release a number of molecules, some of which appear to be immunomodulatory/suppressive, into the host environment. Here we demonstrate that ES-62, a phosphorylcholine-containing glycoprotein released by the rodent filarial parasite Acanthocheilonema viteae, interferes with activation of B lymphocytes by differential modulation of protein kinase C isoform expression. Indeed, while ES-62 selectively down-regulates expression of the alpha, beta, iota/lambda, delta, and zeta isoforms of PKC, it up-regulates expression of PKC-gamma and -epsilon in B cells. Inhibitor studies suggest that ES-62 appears to promote down-regulation of PKC isoforms mainly by stimulating proteolytic degradation. ES-62 also disrupts the normal activation and nuclear translocation patterns of the alpha and iota/lambda isoforms of PKC following ligation of the Ag receptor. The effects of ES-62 on certain PKC isoforms were found to be modified by coculture with IL-4. Of particular interest was the observation that IL-4 prevented down-regulation of PKC alpha and iota/lambda, isotypes considered to be active in transducing mitogenic signals. Phosphorylcholine-containing secreted products (phosphorylcholine-ES) are also released by human filarial parasites; hence we discuss how these findings may relate to the nature of the human B cell response during filarial infections.