Fetal VDJ gene repertoire in rabbit: evidence for preferential rearrangement of VH1.

B cells in rabbit preferentially utilize the 3'-most VH gene, VH1, in VDJ genes. To determine whether the preferential utilization of VH1 results from preferential rearrangement, we examined VH gene usage in nonproductive VDJ gene rearrangements, genes that would not be influenced by antigen selection. Since nonproductive VDJ gene rearrangements are found infrequently in neonatal and adult rabbits, we examined the VDJ gene rearrangements during early fetal development. According to nested-primer polymerase chain reaction analyses, VDJ genes in fetal liver appeared around day 14 of gestation and nucleotide sequence analyses of VDJ genes cloned from 14- to 28-day-old fetuses showed that many of the genes were nonproductive. We found that most of these nonproductive genes had utilized VH1 indicating to us that the preferential utilization of VH1 is due to preferential rearrangement. We compared the nucleotide sequence of the promoter region of VH1 with sequences of several other unutilized and infrequently utilized VH genes and found that the core transcriptional factor motifs were similar in all VH promoters examined. We suggest that transcriptional activity of the VH1 promoter region does not explain the preferential rearrangement of VH1.