{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T11:41:59Z","timestamp":1789731719237,"version":"4.0.1"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2018,6,22]],"date-time":"2018-06-22T00:00:00Z","timestamp":1529625600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/about_us\/legal\/notices"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Basic Research Program of China","doi-asserted-by":"crossref","award":["2015CB943300"],"award-info":[{"award-number":["2015CB943300"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81373129"],"award-info":[{"award-number":["81373129"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81571529"],"award-info":[{"award-number":["81571529"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["17K08878"],"award-info":[{"award-number":["17K08878"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,6,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>B-1 cells are innate-like B-cell population and produce natural antibodies that contribute to the first line of host defense. There are two subsets of B-1 cells: B-1a and B-1b. B-1a cells are the main producer of poly-reactive and autoreactive natural IgM antibodies, whereas B-1b cells can respond specifically to T-cell-independent antigens. Despite the functional significance of B-1a and B-1b cells, little information is available about what regulates the development of these two subsets. We found that Kelch-like protein 14 (KLHL14) was expressed at high levels in B cells but only at low levels in a few non-lymphoid tissues. Although mice lacking KLHL14 died right after birth, the heterozygotes developed normally with no gross abnormalities by appearance. B-cell development in the bone marrow and maturation and activation in the spleen were not affected in the heterozygous mice. However, the number of peritoneal B-1a cells was significantly reduced while B-1b cells were increased in Klhl14 heterozygous mice compared with wild-type (WT) mice. Consistently, Rag1\u2212\/\u2212 mice reconstituted with Klhl14\u2212\/\u2212 fetal liver cells had a more severe reduction of B-1a and an increase of B-1b cells in the peritoneal cavity. KLHL14 did not affect the turnover or apoptosis of B-1a and B-1b cells in vivo. Moreover, Klhl14\u2212\/\u2212 fetal liver contained a similar proportion and absolute numbers of the B-1 progenitor cells as did WT fetal liver. These results suggest that KLHL14 promotes B-1a development in mice.<\/jats:p>","DOI":"10.1093\/intimm\/dxy033","type":"journal-article","created":{"date-parts":[[2018,6,12]],"date-time":"2018-06-12T11:09:43Z","timestamp":1528801783000},"page":"311-318","source":"Crossref","is-referenced-by-count":15,"title":["Kelch-like protein 14 promotes B-1a but suppresses B-1b cell development"],"prefix":"10.1093","volume":"30","author":[{"given":"Shuyin","family":"Li","sequence":"first","affiliation":[{"name":"Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China"},{"name":"State Key Laboratory of AgroBiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Min","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomokatsu","family":"Ikawa","sequence":"additional","affiliation":[{"name":"Laboratory for Immune Regeneration, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoya","family":"Yasuda","sequence":"additional","affiliation":[{"name":"Department of Computational Intelligence and Systems Science, Tokyo Institute of Technology, Yokohama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan-Qing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Fudan University, Shanghai, China"},{"name":"Institute of Acupuncture and Moxibustion, Fudan Institutes of Integrative Medicine, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Tsubata","sequence":"additional","affiliation":[{"name":"Department of Immunology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaofeng","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of AgroBiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Yang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China"},{"name":"Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Fudan University, Shanghai, China"},{"name":"Institute of Acupuncture and Moxibustion, Fudan Institutes of Integrative Medicine, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,6,22]]},"reference":[{"key":"2022071011254859900_CIT0001","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1038\/ni1480","article-title":"Siglec-G is a B1 cell-inhibitory receptor that controls expansion and calcium signaling of the B1 cell population","volume":"8","author":"Hoffmann","year":"2007","journal-title":"Nat. Immunol"},{"key":"2022071011254859900_CIT0002","doi-asserted-by":"crossref","first-page":"2783","DOI":"10.4049\/jimmunol.171.6.2783","article-title":"Notch2 haploinsufficiency results in diminished B1 B cells and a severe reduction in marginal zone B cells","volume":"171","author":"Witt","year":"2003","journal-title":"J. Immunol"},{"key":"2022071011254859900_CIT0003","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1146\/annurev.immunol.20.100301.064833","article-title":"Origins and functions of B-1 cells with notes on the role of CD5","volume":"20","author":"Berland","year":"2002","journal-title":"Annu. Rev. Immunol"},{"key":"2022071011254859900_CIT0004","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/nri2901","article-title":"The double life of a B-1 cell: self-reactivity selects for protective effector functions","volume":"11","author":"Baumgarth","year":"2011","journal-title":"Nat. Rev. Immunol"},{"key":"2022071011254859900_CIT0005","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.immuni.2011.11.017","article-title":"B-1 B cell development in the fetus and adult","volume":"36","author":"Montecino-Rodriguez","year":"2012","journal-title":"Immunity"},{"key":"2022071011254859900_CIT0006","doi-asserted-by":"crossref","first-page":"2749","DOI":"10.4049\/jimmunol.177.5.2749","article-title":"B-1 B cell development","volume":"177","author":"Hardy","year":"2006","journal-title":"J. Immunol"},{"key":"2022071011254859900_CIT0007","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":"2022071011254859900_CIT0008","doi-asserted-by":"crossref","first-page":"3053","DOI":"10.1084\/jem.20080979","article-title":"Dual role for B-1a cells in immunity to influenza virus infection","volume":"205","author":"Choi","year":"2008","journal-title":"J. Exp. Med"},{"key":"2022071011254859900_CIT0009","doi-asserted-by":"crossref","first-page":"2978","DOI":"10.1002\/eji.201445146","article-title":"Perspectives on fetal derived CD5+ B1 B cells","volume":"45","author":"Hardy","year":"2015","journal-title":"Eur. J. Immunol"},{"key":"2022071011254859900_CIT0010","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.immuni.2005.04.011","article-title":"B-1a and B-1b cells exhibit distinct developmental requirements and have unique functional roles in innate and adaptive immunity to S. pneumoniae","volume":"23","author":"Haas","year":"2005","journal-title":"Immunity"},{"key":"2022071011254859900_CIT0011","doi-asserted-by":"crossref","first-page":"3277","DOI":"10.4049\/jimmunol.1001792","article-title":"Siglec-G regulates B1 cell survival and selection","volume":"185","author":"Jellusova","year":"2010","journal-title":"J. Immunol"},{"key":"2022071011254859900_CIT0012","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.autrev.2005.10.007","article-title":"Role of B-1a cells in autoimmunity","volume":"5","author":"Duan","year":"2006","journal-title":"Autoimmun. Rev"},{"key":"2022071011254859900_CIT0013","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1007\/s00281-004-0185-z","article-title":"Natural antibodies and the autoimmunity of atherosclerosis","volume":"26","author":"Binder","year":"2005","journal-title":"Springer Semin. Immunopathol"},{"key":"2022071011254859900_CIT0014","doi-asserted-by":"crossref","first-page":"535","DOI":"10.3389\/fimmu.2014.00535","article-title":"B1b cells recognize protective antigens after natural infection and vaccination","volume":"5","author":"Cunningham","year":"2014","journal-title":"Front. Immunol"},{"key":"2022071011254859900_CIT0015","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.1002\/eji.201243070","article-title":"B-1-cell subpopulations contribute differently to gut immunity","volume":"43","author":"Roy","year":"2013","journal-title":"Eur. J. Immunol"},{"key":"2022071011254859900_CIT0016","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1016\/j.mod.2009.07.006","article-title":"Klhl31 is associated with skeletal myogenesis and its expression is regulated by myogenic signals and Myf-5","volume":"126","author":"Abou-Elhamd","year":"2009","journal-title":"Mech. Dev"},{"key":"2022071011254859900_CIT0017","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1073\/pnas.0706729105","article-title":"Specific expression of long noncoding RNAs in the mouse brain","volume":"105","author":"Mercer","year":"2008","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2022071011254859900_CIT0018","doi-asserted-by":"crossref","first-page":"21765","DOI":"10.1074\/jbc.M109.004838","article-title":"Printor, a novel TorsinA-interacting protein implicated in dystonia pathogenesis","volume":"284","author":"Giles","year":"2009","journal-title":"J. Biol. Chem"},{"key":"2022071011254859900_CIT0019","doi-asserted-by":"crossref","first-page":"294","DOI":"10.4049\/jimmunol.1000371","article-title":"A role for lysosomal-associated protein transmembrane 5 in the negative regulation of surface B cell receptor levels and B cell activation","volume":"185","author":"Ouchida","year":"2010","journal-title":"J. Immunol"},{"key":"2022071011254859900_CIT0020","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1111\/j.1365-2249.2007.03337.x","article-title":"Clinical significance of autoantibodies recognizing Sj\u00f6gren\u2019s syndrome A (SSA), SSB, calpastatin and alpha-fodrin in primary Sj\u00f6gren\u2019s syndrome","volume":"148","author":"Go\u00ebb","year":"2007","journal-title":"Clin. Exp. Immunol"},{"key":"2022071011254859900_CIT0021","doi-asserted-by":"crossref","first-page":"E2699","DOI":"10.1073\/pnas.1210706109","article-title":"Critical role of the IgM Fc receptor in IgM homeostasis, B-cell survival, and humoral immune responses","volume":"109","author":"Ouchida","year":"2012","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2022071011254859900_CIT0022","doi-asserted-by":"crossref","first-page":"15882","DOI":"10.1073\/pnas.1206567109","article-title":"Altered Ig levels and antibody responses in mice deficient for the Fc receptor for IgM (Fc\u03bcR)","volume":"109","author":"Honjo","year":"2012","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2022071011254859900_CIT0023","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/ni1301","article-title":"Identification of a B-1 B cell-specified progenitor","volume":"7","author":"Montecino-Rodriguez","year":"2006","journal-title":"Nat. Immunol"},{"key":"2022071011254859900_CIT0024","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/j.immuni.2016.07.014","article-title":"Cellular barcoding links B-1a B cell potential to a fetal hematopoietic stem cell state at the single-cell level","volume":"45","author":"Kristiansen","year":"2016","journal-title":"Immunity"},{"key":"2022071011254859900_CIT0025","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1038\/leu.2014.264","article-title":"The mutational pattern of primary lymphoma of the central nervous system determined by whole-exome sequencing","volume":"29","author":"Vater","year":"2015","journal-title":"Leukemia"},{"key":"2022071011254859900_CIT0026","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.17983","article-title":"Structures of TorsinA and its disease-mutant complexed with an activator reveal the molecular basis for primary dystonia","volume":"5","author":"Demircioglu","year":"2016","journal-title":"Elife"},{"key":"2022071011254859900_CIT0027","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1126\/science.1215173","article-title":"Innate response activator B cells protect against microbial sepsis","volume":"335","author":"Rauch","year":"2012","journal-title":"Science"},{"key":"2022071011254859900_CIT0028","doi-asserted-by":"crossref","first-page":"2756","DOI":"10.4049\/jimmunol.1202697","article-title":"B1a cells enhance susceptibility to infection with virulent Francisella tularensis via modulation of NK\/NKT cell responses","volume":"190","author":"Crane","year":"2013","journal-title":"J. Immunol"},{"key":"2022071011254859900_CIT0029","doi-asserted-by":"crossref","first-page":"e28","DOI":"10.1161\/CIRCRESAHA.117.306044","article-title":"B-1b cells secrete atheroprotective IgM and attenuate atherosclerosis","volume":"117","author":"Rosenfeld","year":"2015","journal-title":"Circ. Res"},{"key":"2022071011254859900_CIT0030","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1084\/jem.20101715","article-title":"B cells enhance early innate immune responses during bacterial sepsis","volume":"208","author":"Kelly-Scumpia","year":"2011","journal-title":"J. Exp. Med"},{"key":"2022071011254859900_CIT0031","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1038\/ni.2685","article-title":"Nck-mediated recruitment of BCAP to the BCR regulates the PI(3)K-Akt pathway in B cells","volume":"14","author":"Castello","year":"2013","journal-title":"Nat. Immunol"},{"key":"2022071011254859900_CIT0032","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1093\/intimm\/dxt042","article-title":"A role for CMTM7 in BCR expression and survival in B-1a but not B-2 cells","volume":"26","author":"Zhang","year":"2014","journal-title":"Int. Immunol"},{"key":"2022071011254859900_CIT0033","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1126\/science.286.5446.1949","article-title":"Requirement for B cell linker protein (BLNK) in B cell development","volume":"286","author":"Pappu","year":"1999","journal-title":"Science"},{"key":"2022071011254859900_CIT0034","doi-asserted-by":"crossref","first-page":"10836","DOI":"10.1038\/ncomms10836","article-title":"EAF2 mediates germinal centre B-cell apoptosis to suppress excessive immune responses and prevent autoimmunity","volume":"7","author":"Li","year":"2016","journal-title":"Nat. Commun"},{"key":"2022071011254859900_CIT0035","doi-asserted-by":"crossref","first-page":"160","DOI":"10.3389\/fimmu.2018.00160","article-title":"Fc\u00b5 receptor promotes the survival and activation of marginal zone B cells and protects mice against bacterial sepsis","volume":"9","author":"Liu","year":"2018","journal-title":"Front. Immunol"}],"container-title":["International Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/intimm\/article-pdf\/30\/7\/311\/44800067\/dxy033.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/intimm\/article-pdf\/30\/7\/311\/44800067\/dxy033.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,10]],"date-time":"2022-07-10T11:26:13Z","timestamp":1657452373000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/intimm\/article\/30\/7\/311\/5043145"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,6,22]]},"references-count":35,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2018,6,22]]},"published-print":{"date-parts":[[2018,6,26]]}},"URL":"https:\/\/doi.org\/10.1093\/intimm\/dxy033","relation":{},"ISSN":["0953-8178","1460-2377"],"issn-type":[{"value":"0953-8178","type":"print"},{"value":"1460-2377","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2018,7]]},"published":{"date-parts":[[2018,6,22]]}}}