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 molecu les, 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 Acan thocheilonema viteae, interferes with activation of B lymphocytes by d ifferential modulation of protein kinase C isoform expression. Indeed, while ES-62 selectively down-regulates expression of the alpha, beta, iota/lambda, delta, and zeta 5 isoforms of PKC, it up-regulates expre ssion of PKC-gamma and -epsilon in B cells. Inhibitor studies suggest that ES-62 appears to promote down-regulation of PKC isoforms mainly b y stimulating proteolytic degradation. ES-62 also disrupts the normal activation and nuclear translocation patterns of the a 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 preven ted down-regulation of PKC a and Jh, isotypes considered to be active in transducing mitogenic signals. Phosphorylcholine-containing secrete d products (phosphorylcholine-ES) are also released by human filarial parasites; hence we discuss how these findings may relate to the natur e of the human B cell response during filarial infections.