THE UTILIZATION OF INDIVIDUAL V(H) EXONS IN THE PRIMARY REPERTOIRE OFADULT BALB C MICE/

The utilization of V(H) gene families is severely biased during fetal development, such that D-region proximal V(H) genes are overrepresente d. After birth the V(H) repertoire becomes more equally representative of the total inherited set of functional V(H) genes. To investigate t he extent of this normalization process, we have determined the relati ve utilization of individual V(H) exons in the pre-immune repertoire o f adult BALB/c spleen cells. Large samples of IgM heavy chain transcri pts from polyclonally activated B cells were captured in a cDNA phage library and screened by hybridization using highly specific oligonucle otide probes. These studies revealed that the utilization of particula r V(H) exons can differ by an order of magnitude. Significantly, the V (H) genes most underrepresented in the pre-immune repertoire are locat ed in the region of the Igh locus most distal to the DJhCh region. We suggest that the chromosomal position of a particular V(H) gene may in fluence its utilization and that the normalization of the adult repert oire is incomplete.