Antibody repertoire development in the sheep

The model of immunoglobulin (Ig) repertoire diversification in sheep has evolved dramatically in recent years. A process thought to involve the rearrangement of a very limited number of variable (V), diversity (D) and joining (J) segments followed by intense, antigen (Ag)-independent, somatic hypermutation is now known to be less recombinatorially restrictive and to involve fewer mutational events. Although mutation rates are now lower than previously thought, the somatic hypermutation process itself is no less critical to the development of the primary Ig repertoire in sheep. Recent studies have shown that those B cells that fail to mutate will die via apoptosis. Much of the V(D)J rearrangement is thought to occur in the fetal liver and spleen prior to development of the ileal Peyer's patch (PP) at approximately day 100 of gestation. Although de novo Ig rearrangement likely does not occur in the ileal PP, this tissue is a site of massive B-cell proliferation, selection and Ig diversification through somatic hypermutation.