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The Journal of Immunology, Vol 151, Issue 10 5364-5375, Copyright © 1993 by American Association of Immunologists

ARTICLES

The utilization of individual VH exons in the primary repertoire of adult BALB/c mice

KM Sheehan, CA Mainville, S Willert and PH Brodeur
Immunology Program, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA 02111.

The utilization of VH gene families is severely biased during fetal development, such that D-region proximal VH genes are overrepresented. After birth the VH repertoire becomes more equally representative of the total inherited set of functional VH genes. To investigate the extent of this normalization process, we have determined the relative utilization of individual VH exons in the pre-immune repertoire of adult BALB/c spleen cells. Large samples of IgM heavy chain transcripts from polyclonally activated B cells were captured in a cDNA phage library and screened by hybridization using highly specific oligonucleotide probes. These studies revealed that the utilization of particular VH exons can differ by an order of magnitude. Significantly, the VH genes most under-represented in the pre-immune repertoire are located in the region of the Igh locus most distal to the DjhCh region. We suggest that the chromosomal position of a particular VH gene may influence its utilization and that the normalization of the adult repertoire is incomplete.


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