HEAVY-CHAIN VARIABLE (V(H)) REGION DIVERSITY GENERATED BY V(H) GENE REPLACEMENT IN THE PROGENY OF A SINGLE PRECURSOR CELL TRANSFORMED WITH A TEMPERATURE-SENSITIVE MUTANT OF ABELSON MURINE LEUKEMIA-VIRUS

Sequence analysis of a large number of DNA clones containing a functional heavy chain variable, diversity, and joining (V(H)DJ(H)) complex generated by V(H) to V(H)DJ(H) joining (V(H) gene replacement) in the progeny derived from a common precursor cell transformed with a temperature-sensitive (ts) Abelson murine leukemia virus (A-MuLV) indicates that endogenous V(H) gene replacement in vitro generates immunoglobulin gene joints distinct from those generated by the usual V(H) to DJ(H) joining. Such joints keep the pentamer CAAGA at the 3' end of the donor V(H) segment and lack a recognizable D segment, as can be seen also in vivo. The results suggest that V(H) gene replacement participates in generating V(H) region diversity in vivo, as previously postulated. During the joining process, a unique V(H) gene was selected in all progeny cells, together with a single A nucleotide dominantly added to the junctional boundaries. The basis of these regulatory processes is discussed.