Representation of rearranged V{sub H} gene segments in the human adult antibody repertoire
Journal Article
·
· Journal of Immunology
OSTI ID:91156
- Virginia Mason Research Center, Seattle, WA (United States)
- Fred Hutchinson Cancer Research Center, Seattle, WA (United States); and others
The heavy chain variable region composition of the human adult Ab repertoire is poorly defined, but recent evidence suggests that peripheral blood B cells may express a nonstochastic assortment of V{sub H} genes. In this study, the contribution of individual V{sub H} gene segments to the human Ab repertoire has been assessed. As a measure of V{sub H} gene utilization, the frequency of occurrence of eight individual V{sub H}3 gene segments contained in rearrangements was assessed in the peripheral blood B cells of two adult subjects. In addition, the frequency of occurrence of rearrangements containing nine individual V{sub H}4 gene segments was analyzed in one of the subjects. More than 2500 independent rearrangements were analyzed. For controls, amplifications and subsequent identification of nonrearranged V{sub H}3 and V{sub H}4 genes from the same individuals were also performed. The results of this germ-line analysis indicated that approximately 25 V{sub H}3 gene segments and nine V{sub H}4 gene segments could be amplified quantitatively. However, usage of elements was not uniform; one V{sub H}3 element, V3-23, and one V{sub H}4 element, V4-34, were represented among rearrangements more frequently than were other members of their respective families. This pattern of V{sub H} utilization was apparent in B cells isolated from the same subject after an 8-mo interval, indicating the relative stability of the repertoire over time. These results indicate that the adult human Ab repertoire is dominated by a few V{sub H} genes demonstrating a pattern of nonrandom utilization that could involve preferential rearrangement and/or receptor-independent selection. 52 refs., 5 figs., 2 tabs.
- OSTI ID:
- 91156
- Journal Information:
- Journal of Immunology, Journal Name: Journal of Immunology Journal Issue: 8 Vol. 154; ISSN JOIMA3; ISSN 0022-1767
- Country of Publication:
- United States
- Language:
- English
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