NONSTOCHASTIC UTILIZATION OF IG-V REGION GENES IN UNSELECTED HUMAN PERIPHERAL B-CELLS

Limited evidence based on a few subjects suggests that human periphera l blood B cells may express a non-stochastic assortment of V region ge nes. To determine if non-stochastic utilization was a generally applic able rule, the identities of rearranged V region gene segments were de termined in unselected peripheral blood B cells from 12 subjects (five male, seven female), ranging in age from 35 to 72 years. The analysis was limited to V region genes belonging to the V(H)3 gene family. Mor e than 4500 independent V(H)3-containing rearrangements were analysed. The frequency of occurrence of eight individual V(H)3 gene segments c ontained in rearrangements was assessed using gene specific oligonucle otide probes. Usage of elements was not uniform. Three elements, which have been known to encode autoantibodies as well as to be frequently rearranged during fetal development, were represented among rearrangem ents more frequently than were other members of the V(H)3 family, and in aggregate, accounted for the majority of rearrangements. These thre e predominant loci are clustered in an 80 kb region suggesting an infl uence of chromosomal location on efficiency of rearrangement. The resu lts document a clear, statistically significant, preference for the oc currence of specific V region genes among rearrangements. The modest a mount of variation observed between subjects was not associated with e ither age or gender. Duplications which increased gene dose may have c ontributed to increased gene usage. These data indicate that, in cauca sians, the immunoglobulin rearrangements in adult human B cells are do minated by a few heavy chain V region genes to the exclusion of other putatively equally functional genes. Thus, the conventional notion tha t the adult repertoire is normalized with respect to family complexity is not confirmed by analysis of individual V-H genes. Copyright (C) 1 996 Elsevier Science Ltd.