Although only a small proportion of mouse and human B cells are CD5(+), most adult rabbit B cells express CD5. However, CD5 was not detectable on the majority of B cells in neonatal appendix 1 and 3days after birth. Cell trafficking studies demonstrated that CD5(+) and CD5(-) CD62L(+) B cells from bone marrow migrated into appendix. There, CD5(+) B cells were preferentially expanded and predominated by approximately 2weeks of age. In mutant ali/ali rabbits, VHa2(+) B cells develop through gene conversion-like alteration of rearranged VH genes upstream of deleted VH1a2. Correlated appearance of individual CD5(+) germinal centers and VHa2(+) B-cells in mutant appendix suggests that CD5 binding positively selects cells with a2(+) framework regions that bind CD5. Following negative and positive selection, cells with diversified rearranged heavy- and light-chain sequences exit appendix, migrate to peripheral tissues and constitute the preimmune repertoire of CD5(+) B cells that encounter foreign antigens.