Technical Abstract: Usage of variable region gene segments during development of the antibody repertoire in mammals is unresolved in part because of the complexity of the locus in mice and humans and the difficulty of distinguishing intrinsic from extrinsic influences in these species. We have addressed this using a highly controlled animal model with a manageable number of VH genes, two functional DH genes and one JH. We tracked VH usage in DNA rearrangements and in VDJ transcripts throughout 75 days of gestation (DG), thereafter in isolator piglets reared germfree, colonized and virus-infected and in conventional adults. We show that the pattern of using five VH genes to form >70% of the pre-immune repertoire persists postnatally in all treatment groups. The repertoire diversification index (RDI) after birth parallels the increased frequency of somatic hypermutation (SHM) in the same small constellation of major VH genes that formed the pre-immune repertoire. This was also paralleled by an increase in serum Ig levels. The frequency of SHM in germfree isolators piglets was the same as in fetal animals. We conclude that: (a) an intrinsic program controls VH gene usage that is independent of age and environmental antigens and (b) repertoire diversification is by SHM of the major genes of the pre-immune repertoire not by the use of other VH genes in the genome. These findings leave unexplained why: (a) the genomic repertoire of eutherian mammals contains so many seldom-used VH genes and (b) certain VH genes are the chosen few.