The most D-proximal functional V(H) gene, V(H)81X, is preferentially expressed in the mouse fetal B cell repertoire; however, it is expressed in few a cells in the adult. To determine when V(H)81X gene expression affects size and phenotype of particular stages in a cell differentiation, transgenic mice have been developed expressing a germline fetal liver-derived V(H)81X-μ rearrangement. Comparative analysis of a lymphopoiesis reveals similarities and differences between fetal liver and adult bone marrow which pinpoint developmental stages in mice during which V(H)81X-expressing B cell progenitors expand or deplete compartment sizes. These include a similar reduction in c-kitR+ and establishment of a predominant CD43(low)/HSA(high) phenotype within the B220+CD43+ compartment which is dependent on the association of the transgene with λ5. In contrast, the CD43- pre-B and immature B cell compartments are expanded in the fetus but not in the adult. In addition, there are other factors that later disfavor the survival of V(H)81X-expressing B1 and B2 cells. Thus the failure to detect V(H)81X-bearing B cells in the adult is the result of a multistep selection process occurring at all stages during a repertoire expansion.