Suppression of antibody responses to the acetylcholine receptor by natural antibodies

Some relationships between "natural" physiological autoreactivity and antibody responses against the acetylcholine receptor (AChR) were investigated. Collections of unselected monoclonal antibodies were derived from nonmanipulated newborn mice of susceptible (BALB.B) and resistant (BALB/c) mouse strains, and screened for reactivity with heterologous AChR. Five in 200 BALB/c but none in 200 BALB.B clones were found reactive. Four of these anti-AChR antibodies were analyzed for connectivity to nine other antibodies in the same collection, and three of them found to react with a particular natural anti-idiotype. The functional in vivo significance of such natural idiotypic complementarities in the anti-AChR response could then be investigated. Treatment of BALB/c newborn animals with low (100 ng) or high (100 micrograms) doses of natural anti-idiotype significantly suppressed their anti-AChR antibody response when immunized as adults. The utilization of natural anti-idiotype reagents with broad reactivity patterns might overcome the known idiotype heterogeneity of the autoimmune antibody response to AChR and provide a strategy in prophylactic and therapeutic manipulation of disease development.