{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:50:55Z","timestamp":1790805055513,"version":"4.1.0"},"reference-count":29,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"72","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Immunol."],"published-print":{"date-parts":[[2022,6,24]]},"abstract":"<jats:p>\n            The SKIV2L RNA exosome is an evolutionarily conserved RNA degradation complex in the eukaryotes. Mutations in the\n            <jats:italic>SKIV2L<\/jats:italic>\n            gene are associated with a severe inherited disorder, trichohepatoenteric syndrome (THES), with multisystem involvement but unknown disease mechanism. Here, we reported a THES patient with\n            <jats:italic>SKIV2L<\/jats:italic>\n            mutations showing severe primary B cell immunodeficiency, hypogammaglobulinemia, and kappa-restricted plasma cell dyscrasia but normal T cell and NK cell function. To corroborate these findings, we made B cell\u2013specific\n            <jats:italic>Skiv2l<\/jats:italic>\n            knockout mice (\n            <jats:italic>Skiv2l<\/jats:italic>\n            <jats:sup>fl\/fl<\/jats:sup>\n            <jats:italic>Cd79a-Cre<\/jats:italic>\n            ), which lacked both conventional B-2 and innate-like B-1 B cells in the periphery and secondary lymphoid organs. This was linked to a requirement of SKIV2L RNA exosome activity in the bone marrow during early B cell development at the pro\u2013B cell to large pre\u2013B cell transition. Mechanistically,\n            <jats:italic>Skiv2l<\/jats:italic>\n            -deficient pro\u2013B cells exhibited cell cycle arrest and DNA damage. Furthermore, loss of Skiv2l led to substantial out-of-frame V(D)J rearrangement of immunoglobulin heavy chain and severely reduced surface expression of \u03bcH, both of which are crucial for pre-BCR signaling and proliferative burst during early B cell development. Together, our data demonstrated a crucial role for SKIV2L RNA exosome in early B cell development in both human and mice by ensuring proper V(D)J recombination and\n            <jats:italic>Igh<\/jats:italic>\n            expression, which serves as the molecular basis for immunodeficiency associated with THES.\n          <\/jats:p>","DOI":"10.1126\/sciimmunol.abn2888","type":"journal-article","created":{"date-parts":[[2022,6,3]],"date-time":"2022-06-03T17:55:12Z","timestamp":1654278912000},"source":"Crossref","is-referenced-by-count":22,"title":["The mammalian SKIV2L RNA exosome is essential for early B cell development"],"prefix":"10.1126","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2011-7084","authenticated-orcid":true,"given":"Kun","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Immunology, UT Southwestern Medical Center, Dallas, TX, USA."},{"name":"Department of Microbiology, UT Southwestern Medical Center, Dallas, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Immunology, UT Southwestern Medical Center, Dallas, TX, USA."},{"name":"Department of Microbiology, UT Southwestern Medical Center, Dallas, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7167-7359","authenticated-orcid":true,"given":"Jennifer G.","family":"Gill","sequence":"additional","affiliation":[{"name":"Department of Dermatology, UT Southwestern Medical Center, Dallas, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason Y.","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Pathology and the Eugene McDermott Center for Human Growth and Development, UT Southwestern Medical Center, Dallas, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7088-8530","authenticated-orcid":true,"given":"Meghana N.","family":"Sathe","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, UT Southwestern Medical Center, Dallas, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9404-0411","authenticated-orcid":true,"given":"Jyothsna","family":"Gattineni","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, UT Southwestern Medical Center, Dallas, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3493-8772","authenticated-orcid":true,"given":"Tracey","family":"Wright","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, UT Southwestern Medical Center, Dallas, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8035-8165","authenticated-orcid":true,"given":"Christian","family":"Wysocki","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Teresa","family":"de la Morena","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Washington and, Seattle, WA, USA."},{"name":"Seattle Children\u2019s Hospital, Seattle, WA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0637-3989","authenticated-orcid":true,"given":"Nan","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Immunology, UT Southwestern Medical Center, Dallas, TX, USA."},{"name":"Department of Microbiology, UT Southwestern Medical Center, Dallas, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1964"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2014.01.011"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2015.15"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.07.017"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.02.009"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2010.02.010"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23418"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01036"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-017-0460-0"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2003.07.003"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2018.12.001"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-021-01142-2"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2491"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1261\/rna.064626.117"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.1711560412"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.36.11.1531"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0609.1966.tb02371.x"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinre.2014.05.008"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.12.030"},{"key":"e_1_3_3_21_2","first-page":"1097","article-title":"RRP6\/EXOSC10 is required for the repair of DNA double-strand breaks by homologous recombination","volume":"128","author":"Marin-Vicente C.","year":"2015","unstructured":"C. Marin-Vicente, J. Domingo-Prim, A. B. Eberle, N. Visa, RRP6\/EXOSC10 is required for the repair of DNA double-strand breaks by homologous recombination. J. Cell Sci. 128, 1097\u20131107 (2015).","journal-title":"J. Cell Sci."},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-10153-9"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.01.001"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13580"},{"key":"e_1_3_3_25_2","doi-asserted-by":"crossref","first-page":"abn2738","DOI":"10.1126\/sciimmunol.abn2738","article-title":"RNA exosome drives early B cell development via non-coding RNA processing mechanisms","volume":"07","author":"Laffleur B.","year":"2022","unstructured":"B. Laffleur, C. R. Batista, W. Zhang, J. Lim, B. Yang, D. Rossille, L. Wu, J. Estrella, G. Rothschild, E. Pefanis, U. Basu, RNA exosome drives early B cell development via non-coding RNA processing mechanisms. Sci. 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