Rabbit appendix: a site of development and selection of the B cell repertoire.

As early as 1963, it was proposed that the rabbit appendix was a homologue of the chicken bursa of Fabricius (ARCHER et al. 1963). The finding that the young rabbit appendix was thymus independent contributed to the concept of central primary lymphoid tissue. Today we know that appendix is a site that generates the high copy number primary repertoire through diversification of rearranged VH genes by gene conversion-like and somatic hypermutation mechanisms. Thus the appendix of young rabbits functions as a mammalian bursal equivalent. In the appendix, newly generated B cells also undergo selection processes involving self and foreign antigens and superantigens. Preferential expansion and survival of B cells in normal and mutant ali rabbits based on FR1 and FR3 expression may involve "superantigen"-like interactions with endogenous and exogenous ligands. One endogenous ligand appears to be CD5. Additional ligands may be produced by gut flora. Further studies in the rabbit model are needed to determine the fates of emigrants from primary GALT, their sites of postulated self-renewal in the periphery, and the nature of secondary diversification in secondary germinal centers where populations of B lymphocyte memory cells may develop. These data may also be helpful in understanding how the repertoire of human B cells is formed and how this repertoire might be manipulated for clinical benefit.