Abstract:
:The adult repertoire of antibody specificities is acquired in a developmentally programmed fashion that, in mouse and man, parallels the ordered rearrangement of a limited number of germ-line heavy chain variable region (VH) gene segments during development. It has been hypothesized that this developmental bias is a consequence of gene organization. In the mouse, rearrangement of VH gene segments proximal to the heavy chain joining region (JH) locus precedes rearrangement of genes located more distal to the JH locus. Similarly, in man, two VH elements located proximal to JH are expressed during fetal development. To test further this hypothesis in man, we have determined in a single individual the positions of an additional eight distinct VH elements known to comprise a significant fraction of the human developmental repertoire. These developmentally expressed VH elements were found to be dispersed over a region of 890 kilobases of the VH locus and were interspersed with other VH elements that are not known to be developmentally expressed. Thus, the ordered developmental expression of VH gene segments in man must involve mechanisms beyond physical proximity to the JH locus. Further, these results support the notion that fetal expression of VH gene segments is a regulated process and suggest that this regulation is important in the acquisition of immunocompetence.
journal_name
Proc Natl Acad Sci U S Aauthors
Willems van Dijk K,Milner LA,Sasso EH,Milner ECdoi
10.1073/pnas.89.21.10430keywords:
subject
Has Abstractpub_date
1992-11-01 00:00:00pages
10430-4issue
21eissn
0027-8424issn
1091-6490journal_volume
89pub_type
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