Somatic generation of antigen-receptor diversity: a reprise

Thirty years ago, in his inaugural article entitled 'The somatic generation of immune recognition', Niels Jerne put forward the hypothesis that the pr imary antigen (Ag)-receptor repertoire must be restricted towards self-Ags before Ag-mediated selection. The subsequent discovery that Ag receptors ar e encoded by random rearrangements between discontinuous gene segments was, apparently, at odds with this hypothesis. However, recent findings have be gun to reconcile these two concepts. The recombination process is, in fact, relatively precise, exhibiting marked preferences for some gene segments o ver others, even among members of the same gene family. The result is an in tricately patterned primary repertoire that accommodates both sets of predi ctions, ensuring a balance between the efficiency of selection (requiring l imited diversity) and the complexity of the repertoire (requiring maximum d iversity).