{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T02:26:48Z","timestamp":1789612008759,"version":"build-2803163510"},"reference-count":58,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2014,1,1]],"date-time":"2014-01-01T00:00:00Z","timestamp":1388534400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Although ribosomal proteins facilitate the ribosome\u2019s 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 \u03b1\u03b2 T cell progenitors at the \u03b2-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\u2013B cell stage. Although Rpl22-deficient pro\u2013B 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.<\/jats:p>","DOI":"10.4049\/jimmunol.1402242","type":"journal-article","created":{"date-parts":[[2014,11,22]],"date-time":"2014-11-22T01:18:07Z","timestamp":1416619087000},"page":"200-209","source":"Crossref","is-referenced-by-count":30,"title":["Rpl22 Loss Impairs the Development of B Lymphocytes by Activating a p53-Dependent Checkpoint"],"prefix":"10.1093","volume":"194","author":[{"given":"Shawn P","family":"Fahl","sequence":"first","affiliation":[{"name":"Immune Cell Development and Host Defense Program, Fox Chase Cancer Center , Philadelphia, PA 19111"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan","family":"Harris","sequence":"additional","affiliation":[{"name":"Immune Cell Development and Host Defense Program, Fox Chase Cancer Center , Philadelphia, PA 19111"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis","family":"Coffey","sequence":"additional","affiliation":[{"name":"Immune Cell Development and Host Defense Program, Fox Chase Cancer Center , Philadelphia, PA 19111"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L","family":"Wiest","sequence":"additional","affiliation":[{"name":"Immune Cell Development and Host Defense Program, Fox Chase Cancer Center , Philadelphia, PA 19111"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,1,1]]},"reference":[{"key":"2025031310015407000_r1","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1016\/j.immuni.2007.05.010","article-title":"The transcriptional regulation of B cell lineage commitment","volume":"26","author":"Nutt","year":"2007","journal-title":"Immunity"},{"key":"2025031310015407000_r2","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/j.immuni.2007.05.013","article-title":"The protean nature of cells in the B lymphocyte lineage","volume":"26","author":"Hardy","year":"2007","journal-title":"Immunity"},{"key":"2025031310015407000_r3","doi-asserted-by":"crossref","first-page":"6834","DOI":"10.4049\/jimmunol.167.12.6834","article-title":"Resolution of three nonproliferative immature splenic B cell subsets reveals multiple selection points during peripheral B cell maturation","volume":"167","author":"Allman","year":"2001","journal-title":"J. Immunol."},{"key":"2025031310015407000_r4","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.coi.2008.03.014","article-title":"Peripheral B cell subsets","volume":"20","author":"Allman","year":"2008","journal-title":"Curr. Opin. Immunol."},{"key":"2025031310015407000_r5","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.smim.2008.08.003","article-title":"Gene regulatory networks directing myeloid and lymphoid cell fates within the immune system","volume":"20","author":"Laslo","year":"2008","journal-title":"Semin. Immunol."},{"key":"2025031310015407000_r6","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1038\/ni.1827","article-title":"Role of STAT5 in controlling cell survival and immunoglobulin gene recombination during pro-B cell development","volume":"11","author":"Malin","year":"2010","journal-title":"Nat. Immunol."},{"key":"2025031310015407000_r7","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.coi.2010.02.004","article-title":"STAT5 in B cell development and leukemia","volume":"22","author":"Malin","year":"2010","journal-title":"Curr. Opin. Immunol."},{"key":"2025031310015407000_r8","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1038\/ni1324","article-title":"A unique function for cyclin D3 in early B cell development","volume":"7","author":"Cooper","year":"2006","journal-title":"Nat. Immunol."},{"key":"2025031310015407000_r9","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1038\/ni.1785","article-title":"Ras orchestrates exit from the cell cycle and light-chain recombination during early B cell development","volume":"10","author":"Mandal","year":"2009","journal-title":"Nat. Immunol."},{"key":"2025031310015407000_r10","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/nri3570","article-title":"Orchestrating B cell lymphopoiesis through interplay of IL-7 receptor and pre-B cell receptor signalling","volume":"14","author":"Clark","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"2025031310015407000_r11","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1038\/ni.2887","article-title":"Noncoding RNA and its associated proteins as regulatory elements of the immune system","volume":"15","author":"Turner","year":"2014","journal-title":"Nat. Immunol."},{"key":"2025031310015407000_r12","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1038\/ni.2884","article-title":"Post-transcriptional coordination of immunological responses by RNA-binding proteins","volume":"15","author":"Kafasla","year":"2014","journal-title":"Nat. Immunol."},{"key":"2025031310015407000_r13","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/S0968-0004(96)20011-8","article-title":"Extraribosomal functions of ribosomal proteins","volume":"21","author":"Wool","year":"1996","journal-title":"Trends Biochem. Sci."},{"key":"2025031310015407000_r14","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1186\/1479-7364-4-5-327","article-title":"The other lives of ribosomal proteins","volume":"4","author":"Bhavsar","year":"2010","journal-title":"Hum. Genomics"},{"key":"2025031310015407000_r15","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/S0092-8674(03)00773-6","article-title":"Regulated release of L13a from the 60S ribosomal subunit as a mechanism of transcript-specific translational control","volume":"115","author":"Mazumder","year":"2003","journal-title":"Cell"},{"key":"2025031310015407000_r16","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.molcel.2008.09.019","article-title":"DAPK-ZIPK-L13a axis constitutes a negative-feedback module regulating inflammatory gene expression","volume":"32","author":"Mukhopadhyay","year":"2008","journal-title":"Mol. Cell"},{"key":"2025031310015407000_r17","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.cell.2011.03.028","article-title":"Ribosome-mediated specificity in Hox mRNA translation and vertebrate tissue patterning","volume":"145","author":"Kondrashov","year":"2011","journal-title":"Cell"},{"key":"2025031310015407000_r18","doi-asserted-by":"crossref","first-page":"3196","DOI":"10.1182\/blood-2009-10-178129","article-title":"Ribosomopathies: human disorders of ribosome dysfunction","volume":"115","author":"Narla","year":"2010","journal-title":"Blood"},{"key":"2025031310015407000_r19","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/j.immuni.2007.04.012","article-title":"Ablation of ribosomal protein L22 selectively impairs alphabeta T cell development by activation of a p53-dependent checkpoint","volume":"26","author":"Anderson","year":"2007","journal-title":"Immunity"},{"key":"2025031310015407000_r20","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/0014-5793(87)80761-5","article-title":"Role of acidic phosphoproteins in the partial reconstitution of the active 60 S ribosomal subunit","volume":"216","author":"Lavergne","year":"1987","journal-title":"FEBS Lett."},{"key":"2025031310015407000_r21","doi-asserted-by":"crossref","first-page":"664","DOI":"10.4049\/jimmunol.1100029","article-title":"Developmental arrest of T cells in Rpl22-deficient mice is dependent upon multiple p53 effectors","volume":"187","author":"Stadanlick","year":"2011","journal-title":"J. Immunol."},{"key":"2025031310015407000_r22","doi-asserted-by":"crossref","first-page":"e1003708","DOI":"10.1371\/journal.pgen.1003708","article-title":"The ribosomal protein Rpl22 controls ribosome composition by directly repressing expression of its own paralog, Rpl22l1","volume":"9","author":"O\u2019Leary","year":"2013","journal-title":"PLoS Genet."},{"key":"2025031310015407000_r23","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1016\/0092-8674(92)90030-G","article-title":"RAG-1-deficient mice have no mature B and T lymphocytes","volume":"68","author":"Mombaerts","year":"1992","journal-title":"Cell"},{"key":"2025031310015407000_r24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0960-9822(00)00002-6","article-title":"Tumor spectrum analysis in p53-mutant mice","volume":"4","author":"Jacks","year":"1994","journal-title":"Curr. Biol."},{"key":"2025031310015407000_r25","doi-asserted-by":"crossref","first-page":"5582","DOI":"10.4049\/jimmunol.0901187","article-title":"c-Myb is required for pro-B cell differentiation","volume":"183","author":"Fahl","year":"2009","journal-title":"J. Immunol."},{"key":"2025031310015407000_r26","doi-asserted-by":"crossref","first-page":"2376","DOI":"10.1101\/gad.1836009","article-title":"Ly6d marks the earliest stage of B-cell specification and identifies the branchpoint between B-cell and T-cell development","volume":"23","author":"Inlay","year":"2009","journal-title":"Genes Dev."},{"key":"2025031310015407000_r27","doi-asserted-by":"crossref","first-page":"e78408","DOI":"10.1371\/journal.pone.0078408","article-title":"Separation of plasmacytoid dendritic cells from B-cell-biased lymphoid progenitor (BLP) and Pre-pro B cells using PDCA-1","volume":"8","author":"Medina","year":"2013","journal-title":"PLoS ONE"},{"key":"2025031310015407000_r28","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1084\/jem.183.1.187","article-title":"A subpopulation of B220+ cells in murine bone marrow does not express CD19 and contains natural killer cell progenitors","volume":"183","author":"Rolink","year":"1996","journal-title":"J. Exp. Med."},{"key":"2025031310015407000_r29","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1084\/jem.173.5.1213","article-title":"Resolution and characterization of pro-B and pre-pro-B cell stages in normal mouse bone marrow","volume":"173","author":"Hardy","year":"1991","journal-title":"J. Exp. Med."},{"key":"2025031310015407000_r30","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.smim.2012.02.001","article-title":"The many roles of IL-7 in B cell development; mediator of survival, proliferation and differentiation","volume":"24","author":"Corfe","year":"2012","journal-title":"Semin. Immunol."},{"key":"2025031310015407000_r31","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.ccr.2009.09.024","article-title":"Signaling to p53: ribosomal proteins find their way","volume":"16","author":"Zhang","year":"2009","journal-title":"Cancer Cell"},{"key":"2025031310015407000_r32","doi-asserted-by":"crossref","first-page":"e4152","DOI":"10.1371\/journal.pone.0004152","article-title":"Loss of ribosomal protein L11 affects zebrafish embryonic development through a p53-dependent apoptotic response","volume":"4","author":"Chakraborty","year":"2009","journal-title":"PLoS ONE"},{"key":"2025031310015407000_r33","doi-asserted-by":"crossref","first-page":"5228","DOI":"10.1182\/blood-2008-01-132290","article-title":"Ribosomal protein S19 deficiency in zebrafish leads to developmental abnormalities and defective erythropoiesis through activation of p53 protein family","volume":"112","author":"Danilova","year":"2008","journal-title":"Blood"},{"key":"2025031310015407000_r34","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.devcel.2013.01.018","article-title":"Control of hematopoietic stem cell emergence by antagonistic functions of ribosomal protein paralogs","volume":"24","author":"Zhang","year":"2013","journal-title":"Dev. Cell"},{"key":"2025031310015407000_r35","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1084\/jem.194.8.1151","article-title":"Homeostasis of peripheral B cells in the absence of B cell influx from the bone marrow","volume":"194","author":"Hao","year":"2001","journal-title":"J. Exp. Med."},{"key":"2025031310015407000_r36","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1038\/nri799","article-title":"Marginal-zone B cells","volume":"2","author":"Martin","year":"2002","journal-title":"Nat. Rev. Immunol."},{"key":"2025031310015407000_r37","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/ni1290","article-title":"Mechanistic basis of pre-T cell receptor-mediated autonomous signaling critical for thymocyte development","volume":"7","author":"Yamasaki","year":"2006","journal-title":"Nat. Immunol."},{"key":"2025031310015407000_r38","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1038\/nri2491","article-title":"Regulation of B-cell proliferation and differentiation by pre-B-cell receptor signalling","volume":"9","author":"Herzog","year":"2009","journal-title":"Nat. Rev. Immunol."},{"key":"2025031310015407000_r39","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/79782","article-title":"A cellular calculus for signal integration by T cells","volume":"1","author":"Gett","year":"2000","journal-title":"Nat. Immunol."},{"key":"2025031310015407000_r40","doi-asserted-by":"crossref","first-page":"5032","DOI":"10.1073\/pnas.0700026104","article-title":"A model of immune regulation as a consequence of randomized lymphocyte division and death times","volume":"104","author":"Hawkins","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025031310015407000_r41","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1016\/j.immuni.2012.08.020","article-title":"\u03b2-Selection-induced proliferation is required for \u03b1\u03b2 T cell differentiation","volume":"37","author":"Kreslavsky","year":"2012","journal-title":"Immunity"},{"key":"2025031310015407000_r42","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1084\/jem.191.1.23","article-title":"Precursor B cell receptor-dependent B cell proliferation and differentiation does not require the bone marrow or fetal liver environment","volume":"191","author":"Rolink","year":"2000","journal-title":"J. Exp. Med."},{"key":"2025031310015407000_r43","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1073\/pnas.98.4.1745","article-title":"Induction of pre-B cell proliferation after de novo synthesis of the pre-B cell receptor","volume":"98","author":"Hess","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025031310015407000_r44","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1038\/ncb1858","article-title":"Absence of nucleolar disruption after impairment of 40S ribosome biogenesis reveals an rpL11-translation-dependent mechanism of p53 induction","volume":"11","author":"Fumagalli","year":"2009","journal-title":"Nat. Cell Biol."},{"key":"2025031310015407000_r45","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/S1535-6108(03)00134-X","article-title":"Regulation of HDM2 activity by the ribosomal protein L11","volume":"3","author":"Lohrum","year":"2003","journal-title":"Cancer Cell"},{"key":"2025031310015407000_r46","doi-asserted-by":"crossref","first-page":"44475","DOI":"10.1074\/jbc.M403722200","article-title":"Inhibition of MDM2-mediated p53 ubiquitination and degradation by ribosomal protein L5","volume":"279","author":"Dai","year":"2004","journal-title":"J. Biol. Chem."},{"key":"2025031310015407000_r47","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.molcel.2008.08.031","article-title":"Mdm2 regulates p53 mRNA translation through inhibitory interactions with ribosomal protein L26","volume":"32","author":"Ofir-Rosenfeld","year":"2008","journal-title":"Mol. Cell"},{"key":"2025031310015407000_r48","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.cell.2005.07.034","article-title":"Regulation of p53 translation and induction after DNA damage by ribosomal protein L26 and nucleolin","volume":"123","author":"Takagi","year":"2005","journal-title":"Cell"},{"key":"2025031310015407000_r49","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.1101\/gad.10.16.2038","article-title":"V(D)J recombination activates a p53-dependent DNA damage checkpoint in scid lymphocyte precursors","volume":"10","author":"Guidos","year":"1996","journal-title":"Genes Dev."},{"key":"2025031310015407000_r50","doi-asserted-by":"crossref","first-page":"1923","DOI":"10.1084\/jem.183.4.1923","article-title":"p53 prevents maturation to the CD4+CD8+ stage of thymocyte differentiation in the absence of T cell receptor rearrangement","volume":"183","author":"Jiang","year":"1996","journal-title":"J. Exp. Med."},{"key":"2025031310015407000_r51","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/S1074-7613(00)80084-9","article-title":"Pre-TCR signaling and inactivation of p53 induces crucial cell survival pathways in pre-T cells","volume":"11","author":"Haks","year":"1999","journal-title":"Immunity"},{"key":"2025031310015407000_r52","doi-asserted-by":"crossref","first-page":"2484","DOI":"10.1002\/(SICI)1521-4141(199908)29:08<2484::AID-IMMU2484>3.0.CO;2-B","article-title":"Regulation of cell survival during B lymphopoiesis: suppressed apoptosis of pro-B cells in P53-deficient mouse bone marrow","volume":"29","author":"Lu","year":"1999","journal-title":"Eur. J. Immunol."},{"key":"2025031310015407000_r53","doi-asserted-by":"crossref","first-page":"8027","DOI":"10.1128\/jvi.69.12.8027-8034.1995","article-title":"In vitro selection of RNA ligands for the ribosomal L22 protein associated with Epstein-Barr virus-expressed RNA by using randomized and cDNA-derived RNA libraries","volume":"69","author":"Dobbelstein","year":"1995","journal-title":"J. Virol."},{"key":"2025031310015407000_r54","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1038\/nrc2716","article-title":"Tumour suppression by p53: a role for the DNA damage response?","volume":"9","author":"Meek","year":"2009","journal-title":"Nat. Rev. Cancer"},{"key":"2025031310015407000_r55","doi-asserted-by":"crossref","first-page":"30036","DOI":"10.1074\/jbc.M604674200","article-title":"Ribosomal stress couples the unfolded protein response to p53-dependent cell cycle arrest","volume":"281","author":"Zhang","year":"2006","journal-title":"J. Biol. Chem."},{"key":"2025031310015407000_r56","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1016\/j.molimm.2007.07.029","article-title":"The unfolded protein response of B-lymphocytes: PERK-independent development of antibody-secreting cells","volume":"45","author":"Gass","year":"2008","journal-title":"Mol. Immunol."},{"key":"2025031310015407000_r57","doi-asserted-by":"crossref","first-page":"17954","DOI":"10.1074\/jbc.M801395200","article-title":"B- and T-cell development both involve activity of the unfolded protein response pathway","volume":"283","author":"Brunsing","year":"2008","journal-title":"J. Biol. Chem."},{"key":"2025031310015407000_r58","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1172\/JCI200521848","article-title":"The unfolded protein response sensor IRE1alpha is required at 2 distinct steps in B cell lymphopoiesis","volume":"115","author":"Zhang","year":"2005","journal-title":"J. Clin. Invest."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/194\/1\/200\/62233219\/1402242.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/194\/1\/200\/62233219\/1402242.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T06:03:26Z","timestamp":1741845806000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/194\/1\/200\/7967738"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,1,1]]},"references-count":58,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2014,1,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1402242","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2015,1]]},"published":{"date-parts":[[2014,1,1]]}}}