title: Rpl22 Loss Impairs the Development of B Lymphocytes by Activating a p53-Dependent Checkpoint.
abstract: Although ribosomal proteins facilitate the ribosome’s core function of translation, emerging evidence suggests that some ribosomal proteins are also capable of performing tissue-restricted functions either from within specialized ribosomes or from outside of the ribosome. In particular, we have previously demonstrated that germline ablation of the gene encoding ribosomal protein Rpl22 causes a selective and p53-dependent arrest of ab T cell progenitors at the b-selection checkpoint. We have now identified a crucial role for Rpl22 during early B cell development. Germline ablation of Rpl22 results in a reduction in the absolute number of B-lineage progenitors in the bone marrow beginning at the pro–B cell stage. Although Rpl22-deficient pro–B cells are hyporesponsive to IL-7, a key cytokine required for early B cell development, the arrest of B cell development does not result from disrupted IL-7 signaling. Instead, p53 induction appears to be responsible for the developmental defects, as Rpl22 deficiency causes increased expression of p53 and activation of downstream p53 target genes, and p53 deficiency rescues the defect in B cell development in Rpl22-deficient mice. Interestingly, the requirement for Rpl22 in the B cell lineage appears to be developmentally restricted, because Rpl22-deficient splenic B cells proliferate normally in response to Ag receptor and Toll receptor stimuli and undergo normal class-switch recombination. These results indicate that Rpl22 performs a critical, developmentally restricted role in supporting early B cell development by preventing p53 induction.
authors.affiliation: Immune Cell Development and Host Defense Program, Fox Chase Cancer Center, Philadelphia, PA 19111
authors.forename: Shawn P
authors.initials: SP
authors.lastname: Fahl
authors.affiliation: Immune Cell Development and Host Defense Program, Fox Chase Cancer Center, Philadelphia, PA 19111
authors.forename: Bryan
authors.initials: B
authors.lastname: Harris
authors.affiliation: Immune Cell Development and Host Defense Program, Fox Chase Cancer Center, Philadelphia, PA 19111
authors.forename: Francis
authors.initials: F
authors.lastname: Coffey
authors.affiliation: Immune Cell Development and Host Defense Program, Fox Chase Cancer Center, Philadelphia, PA 19111
authors.forename: David L
authors.initials: DL
authors.lastname: Wiest
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D002478:Cells, Cultured; D018398:Homeodomain Proteins / Q000235:genetics; D017578:Immunoglobulin Class Switching / Q000276:immunology; D015851:Interleukin-7 / Q000235:genetics; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D016601:RNA-Binding Proteins / Q000235:genetics*; D012269:Ribosomal Proteins / Q000235:genetics*; D012270:Ribosomes / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics*; D060152:V(D)J Recombination / Q000235:genetics / Q000276:immunology
chemical_list: D018398:Homeodomain Proteins; D015851:Interleukin-7; D016601:RNA-Binding Proteins; C522051:RPL22 protein, mouse; D012269:Ribosomal Proteins; D016159:Tumor Suppressor Protein p53; C064658:RAG-1 protein