Development of tbe antibody repertoire in rabbit: gut-associated lymphoid tissue, microbes, and selection

Rabbits generate their antibody repertoire in three stages, First, a neonat al repertoire is generated by B lymphopoiesis in fetal liver and bone marro w and is limited by preferential V-H gene segment usage. Between 4 and 8 we eks after birth a complex primary antibody repertoire is developed by somat ically diversifying the neonatal repertoire through somatic hypermutation a nd a somatic gene conversion-like mechanism in gut-associated lymphoid tiss ue (GALT). In rabbits, unlike other species. the development of the primary antibody repertoire through somatic diversification of Ig genes appears to be dependent on intestinal microbial nora. The primary antibody repertoire is subsequently modified during antigen-dependent immune responses in whic h VDJ genes further diversify both by somatic hypermutation and by a gene c onversion-like mechanism (the secondary repertoire). During the various sta ges of development, the antibody repertoire is modified and shaped by selec tive processes. In this review. we discuss the roles of GALT, microbes, and B-cell selection in generating antibody diversity in rabbits.