REPRESENTATION OF REARRANGED V-H GENE SEGMENTS IN THE HUMAN ADULT ANTIBODY REPERTOIRE

The heavy chain variable region composition of the human adult Ab repe rtoire is poorly defined, but recent evidence suggests that peripheral blood B cells may express a nonstochastic assortment of V-H genes. In this study, the contribution of individual V-H gene segments to the h uman Ab repertoire has been assessed. As a measure of V-H gene utiliza tion, the frequency of occurrence of eight individual V(H)3 gene segme nts 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(H)4 gene segments was analyzed in one of the subjects. More than 2500 independent rearrangem ents were analyzed. For controls, amplifications and subsequent identi fication of nonrearranged V(H)3 and V(H)4 genes from the same individu als were also performed. The results of this germ-line analysis indica ted that approximately 25 V(H)3 gene segments and nine V(H)4 gene segm ents could be amplified quantitatively. However, usage of elements was not uniform; one V(H)3 element, V3-23, and one V(H)4 element, V4-34, were represented among rearrangements more frequently than were other members of their respective families. This pattern of V-H utilization was apparent in B cells isolated from the same subject after an 8-mo i nterval, indicating the relative stability of the repertoire over time . These results indicate that the adult human Ab repertoire is dominat ed by a few V-H genes demonstrating a pattern of nonrandom utilization that could involve preferential rearrangement and/or receptor-depende nt selection.