DEVELOPMENTALLY CONTROLLED SELECTION OF ANTIBODY GENES - CHARACTERIZATION OF INDIVIDUAL VH7183 GENES AND EVIDENCE FOR STAGE-SPECIFIC SOMATIC DIVERSIFICATION

Nucleotide sequence analysis of a large number of rearranged immunoglobulin heavy chain V region genes allowed the identification of six new members of the V(H)7183 gene family. These six new genes plus the eight previously defined genes agrees with the previously estimated complexity of this gene family. Twelve of these genes were represented among the isolated clones. A comparison of the clones, derived from 1-day- and 14-week-old BALB/c mice, suggested a biased and developmentally controlled V(H)7183 gene utilization. Furthermore, a developmentally controlled, non-random distribution of the functional vs. non-functional V(H)DJ(H) rearrangements was observed among clones utilizing genes of this family, suggesting unsuspected regulatory aspects of Ig rearrangements in the process of B cell differentiation. Finally, a limited junctional diversity was revealed among the neonatal clones as the result of a low frequency of N-sequence addition. A similar discrepancy was also observed between neonatal and adult V(H)J558 clones. In conclusion, these data suggest a programmed generation of B cell diversity similar to what has been observed for the establishment of gamma/delta-T cell repertoires.