Posttranscriptional silencing of VbetaDJbetaCbeta genes contributes to TCRbeta allelic exclusion in mammalian lymphocytes.
Feedback inhibition of V(D)J recombination enforces Ag receptor allelic exclusion in mammalian lymphocytes. Yet, in-frame VbetaDJbeta exons can assemble on both alleles in human and mouse alphabeta T lineage cells. To elucidate mechanisms that enforce TCRbeta allelic exclusion in such cells, we analyzed Vbeta expression and rearrangement in mice containing a functional Vbeta14DJbeta1.5Cbeta1 gene (Vbeta14(NT)) and/or Vbeta8.2DJbeta1.1Cbeta1 transgene (Vbeta8(Tg)). The majority of Vbeta14(NT) and Vbeta8(Tg) alphabeta T lineage cells expressed only Vbeta14(+) or Vbeta8(+) TCRbeta-chains, respectively, and lacked Vbeta rearrangements on wild-type TCRbeta loci. However, endogenous Vbeta rearrangements and alphabeta T lineage cells expressing endogenous Vbetas from wild-type alleles alone or with the prerearranged Vbeta in cell surface TCRbeta-chains were observed in Vbeta14(NT) and Vbeta8(Tg) mice. Although nearly all Vbeta8(Tg):Vbeta14(NT) thymocytes and splenic alphabeta T cells expressed Vbeta8(+) TCRbeta-chains, only half of these lymphocytes expressed Vbeta14(+) TCRbeta-chains, even though similar steady-state levels of Vbeta14(NT) mRNA were expressed in Vbeta8(+)Vbeta14(+) and Vbeta8(+)Vbeta14(-) populations. Our data demonstrated that posttranscriptional silencing of functionally assembled endogenous VbetaDJbetaCbeta genes can enforce TCRbeta allelic exclusion and reveal another mechanism that contributes to the development of lymphocytes with monospecific Ag receptors.
Steinel
Natalie C
NC
Immunology Graduate Group, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Brady
Brenna L
BL
Carpenter
Andrea C
AC
Yang-Iott
Katherine S
KS
Bassing
Craig H
CH
D000483:Alleles; D000818:Animals; D005434:Flow Cytometry; D015329:Gene Rearrangement, T-Lymphocyte; D006825:Hybridomas / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008822:Mice, Transgenic; D034622:RNA Interference; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism*
D016693:Receptors, Antigen, T-Cell, alpha-beta