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Abstract: 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 ∼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. [Copyright &y& Elsevier]