Modulation of granulomatous hypersensitivity. IV. Immunoglobulin and antibody production by vigorous and immunomodulated liver granulomas of Schistosoma mansoni-infected mice.

Abstract

The interlesional production of immunoglobulins and SEA-specific antibodies was examined in vitro in cultured hepatic granulomas isolated from Schistosoma mansoni-infected mice. Vigorous lesions of 8-wk and immunomodulated lesions of 20-wk infected mice were cultured in serum-free medium for 48 hr; the supernatant fluid was concentrated, dialyzed, and tested for immunoglobulins by immunodiffusion. Whereas cultures of vigorous granulomas contained only IgG1, those of immunomodulated lesions yielded IgG1, IgG2a, IgG2b, IgG3, and IgA immunoglobulins. Both types of lesions incorporated 14C-labeled leucine into IgM and IgG class immunoglobulins thus proving intralesional synthesis. The immunoglobulins also had specific anti-SEA activity proven by passive hemagglutination and in vivo PCA test. The kinetics of SEA-specific IgM and IgG antibody-forming granuloma lymphocytes was examined by the plaque assay after the dispersal of the lesions. At 8 wk of the infection the number of IgM antibody-producing lymphocytes was low and that of IgG was negligible. In subsequent weeks both IgM and IgG antibody-forming cells increased in numbers. The IgM producer cells peaked at 12 to 16 wk and by 32 wk they dropped to barely detectable levels. The IgG antibody-producing lymphocytes peaked in numbers in the immunomodulated lesions at 20 wk and also disappeared by 32 wk. The kinetics of the granuloma lymphocytes as well as the magnitude of their response differed from those of splenic cells. Intralesional antibody production may promote antigen sequestration, complex formation, and occasional tissue injury. The participation of locally produced antibodies in the modulation of the granulomatous inflammatory response remains to be established.