Network interactions in Schistosoma japonicum infection. Identification and characterization of a serologically distinct immunoregulatory auto-antiidiotypic antibody population.

This study examined the role of naturally occurring anti-idiotypic antibody (anti-id), specific for epitopes on antibodies to schistosome egg antigens (SEA), in serosuppression during Schistosoma japonicum infection. Three anti-id preparations were obtained from pools of infected serum at 12, 16, and 30 wk of infection. Anti-id (12 wk) bound 36% of labeled anti-SEA antibodies, had an idiotype binding capacity (IBC) of 5 micrograms/ml, and did not suppress SEA-induced proliferation. Anti-id (16 wk) bound 17% of labeled anti-SEA antibodies, had 29 micrograms IBC/ml, and reduced 3H incorporation from 21.4 +/- 0.5 (10 micrograms/ml normal Ig) to 9.1 +/- 1.5 X 10(4) cpm (P less than 0.01). Anti-id (30 wk) bound 66% of labeled anti-SEA antibody, had 84 micrograms IBC/ml, and suppressed 3H incorporation by 88% (4.8 +/- 0.3 X 10(4) cpm, P less than 0.001). Analysis of the serologic reactivity of these three populations of anti-idiotypic antibodies revealed that anti-id (12 wk) described an idiotypic population of anti-SEA molecules containing a minor cross-reactive idiotype (SJ-CRIm). In contrast, anti-id (30 wk) described a serologically distinct, idiotypic population containing a major cross-reactive idiotype of anti-SEA molecules (SJ-CRIM). A monoclonal anti-id, which reacted with greater than 50% of the anti-SEA molecules describing SJ-CRIM, was profoundly suppressive in vitro and reduced granulomatous inflammation around parasite eggs in vivo from 113 X 10(3) micron2 to 23 X 10(3) micron2 (80% suppression, P less than 0.001). These observations suggest that immune network interactions modulate inflammation in chronic murine S. japonicum infection.