Immunoglobulin and T-cell receptor (TCR) genes are and after 28 days no hybrid TCR genes were detectassembled by a site-specific rearrangement known able in lymphocyte DNA. These results show that Tas V(D)J [variable-(diversity)-joining] recombina-cells with a hybrid TCR gene are able to respond tion. These rearrangements occur normally in pre-to mitogen stimulation in vitro, and may have a B-and pre-T-cells using signal sequences adjacent to proliferative disadvantage or are selected against coding exons for immunoglobulin and TCR genes, during prolonged in vitro cultivation. No hybrid TCR respectively. However, aberrant recombination genes were detected in ten proliferating T-cell may result in the generation of hybrid TCR genes clones, indicating that the rate of hybrid TCR gene by joining of TCR-b with TCR-g specific sequences. formation is Γ΅2.0 1 10 08 per cell per cell division. Such hybrid TCR genes occur at a low frequency No hybrid TCR genes were detected in DNA from in peripheral blood lymphocytes (PBL) of healthy B-lymphocytes, sperm, granulocytes, fibroblasts, individuals, and can be detected by PCR amplifica-keratinocytes, and three B-lymphoblastoid ataxia tion. We have determined the in vivo frequency of telangiectasia cell lines. In agreement with previous hybrid Vg-Jb1 TCR (hybrid TCR) genes in lympho-reports, the frequency of hybrid TCR genes in pecyte DNA from 12 healthy individuals. The average ripheral blood DNA from two ataxia telangiectasia frequency was found to be 5.83 in 0.75 1 10 6 patients was found to be more than 15-fold higher PBL, with a threefold difference between the highest than in lymphocytes from normal individuals. These and lowest individual value. The presence of similar data show that formation of hybrid TCR genes is TCR gene rearrangements in individual samples restricted to T-cells in vivo, and occurs at a very low suggests that T-cells with a hybrid TCR gene are frequency, if at all, in proliferating T-cells in vitro, capable of clonal expansion in vivo. The individual and with an increased frequency in patients with hybrid TCR gene frequency remained relatively con-ataxia telangiectasia. Environ. Mol. Mutagen. stant during 72 hours of in vitro cultivation. In long-30:245 -253, 1997