Ablation of ribosomal protein L22 selectively impairs alphabeta T cell development by activation of a p53-dependent checkpoint.
The alphabeta and gammadelta T lineages are thought to arise from a common precursor; however, the regulation of separation and development of these lineages is not fully understood. We report here that development of alphabeta and gammadelta precursors was differentially affected by elimination of ribosomal protein L22 (Rpl22), which is ubiquitously expressed but not essential for translation. Rpl22 deficiency selectively arrested development of alphabeta-lineage T cells at the beta-selection checkpoint by inducing their death. The death was caused by induction of p53 expression, because p53 deficiency blocked death and restored development of Rpl22-deficient thymocytes. Importantly, Rpl22 deficiency led to selective upregulation of p53 in alphabeta-lineage thymocytes, at least in part by increasing p53 synthesis. Taken together, these data indicate that Rpl22 deficiency activated a p53-dependent checkpoint that produced a remarkably selective block in alphabeta T cell development but spared gammadelta-lineage cells, suggesting that some ribosomal proteins may perform cell-type-specific or stage-specific functions.
Anderson
Stephen J
SJ
Division of Immunology and Hematology, Lexicon Genetics, Inc., 8800 Technology Forest Place, The Woodlands, TX 77381, USA.
Lauritsen
Jens Peter Holst
JP
Hartman
Matthew G
MG
Foushee
Ann Marie Digeorge
AM
Lefebvre
Juliette M
JM
Shinton
Susan A
SA
Gerhardt
Brenda
B
Hardy
Richard R
RR
Oravecz
Tamas
T
Wiest
David L
DL
D000818:Animals; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019070:Cell Lineage; D008213:Lymphocyte Activation; D008221:Lymphoid Tissue; D008231:Lymphopenia / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D016601:RNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis; D012269:Ribosomal Proteins / Q000378:metabolism / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D016601:RNA-Binding Proteins; C522051:RPL22 protein, mouse; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D012269:Ribosomal Proteins; D016159:Tumor Suppressor Protein p53