GENES RESPONSIBLE FOR QUANTITATIVE REGULATION OF ANTIBODY-PRODUCTION

Evidence is first presented demonstrating that the individual capacity for antibody responsiveness has an inheritable component. The main ev idence consists of spontaneous mutations causing either immunodeficien cy or predisposition to autoimmunity in human and animals, and the inv olvement of some obvious candidate genes (in particular those belongin g to the highly polymorphic histocompatibility and Igh loci), extensiv ely analyzed in many mouse strain combinations. One finding constantly emerging from these studies is that single gene expression depends on environmental effects, lowering the genotype/phenotype correlation, b ut also on multigenic interactions appearing as background effects. Th e models available for the analysis of this multigenic regulation are discussed with special emphasis on the high and low antibody responder mice produced for this purpose by bidirectional selective breeding. T he major advantage of this model is that the interline difference is h uge and multispecifically expressed. The second part of the review pre sents the recent results on positional mapping of genes with immunomod ulatory effects in this model and in one appropriate recombinant conge nic strain series. This in vivo genetic dissection of antibody respons iveness discriminated the involvement of candidate genes and suggested that unsuspected genes might be identified by means of this wide open search.