Differential activation of transcription versus recombination of transgenic T cell receptor beta variable region gene segments in B and T lineage cells.
We have tested the ability of the T cell receptor beta (TCR-beta) transcriptional enhancer (E beta) to confer transcriptional activation and tissue-specific V(D)J recombination of TCR-beta V, D, and J segments in a transgenic minilocus recombination substrate. We find that the minimal E beta element, as previously shown for a DNA segment that contained the E mu element, promotes a high level of substrate D to J beta rearrangement in both B and T cells, but only promotes V beta to DJ beta rearrangement in T cells. Thus, both the E mu and E beta elements similarly direct V(D)J recombination of this substrate in vivo, supporting a general role for transcriptional enhancers in the normal regulation of this rearrangement process. Surprisingly, however, we found that both the V beta and DJ beta portion of the constructs were transcribed in an enhancer-dependent fashion (conferred by either E mu or E beta) in both B and T lineage cells, including normal precursor B cells propagated in culture. These findings indicate that, at least in some contexts, transcriptional activation, per se, is not sufficient to confer V(D)J recombinational accessibility to a substrate V gene segment.
Okada
A
A
Howard Hughes Medical Institute, Children's Hospital, Boston, Massachusetts 02115.
Mendelsohn
M
M
Alt
F
F
D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D004742:Enhancer Elements, Genetic; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D011995:Recombination, Genetic; D014158:Transcription, Genetic
D016693:Receptors, Antigen, T-Cell, alpha-beta