{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T11:14:26Z","timestamp":1775042066126,"version":"3.50.1"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001691","name":"MEXT | Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["26293062"],"award-info":[{"award-number":["26293062"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"MEXT | Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["18H02610"],"award-info":[{"award-number":["18H02610"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"MEXT | Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["17K17695"],"award-info":[{"award-number":["17K17695"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>CD22 is an inhibitory B cell coreceptor that regulates B cell development and activation by downregulating BCR signaling through activation of SH2-containing protein tyrosine phosphatase-1 (SHP-1). CD22 recognizes \u03b12,6 sialic acid as a specific ligand and interacts with \u03b12,6 sialic acid-containing membrane molecules, such as CD45, IgM, and CD22, expressed on the same cell. Functional regulation of CD22 by these endogenous ligands enhances BCR ligation-induced signaling and is essential for normal B cell responses to Ags. In this study, we demonstrate that CD45 plays a crucial role in CD22-mediated inhibition of BCR ligation-induced signaling. However, disruption of ligand binding of CD22 enhances CD22 phosphorylation, a process required for CD22-mediated signal inhibition, upon BCR ligation in CD45\u2212\/\u2212 as well as wild-type mouse B cells but not in mouse B cells expressing a loss-of-function mutant of SHP-1. This result indicates that SHP-1 but not CD45 is required for ligand-mediated regulation of CD22. We further demonstrate that CD22 is a substrate of SHP-1, suggesting that SHP-1 recruited to CD22 dephosphorylates nearby CD22 as well as other substrates. CD22 dephosphorylation by SHP-1 appears to be augmented by homotypic CD22 clustering mediated by recognition of CD22 as a ligand of CD22 because CD22 clustering increases the number of nearby CD22. Our results suggest that CD22 but not CD45 is an endogenous ligand of CD22 that enhances BCR ligation-induced signaling through SHP-1\u2013mediated dephosphorylation of CD22 in CD22 clusters.<\/jats:p>","DOI":"10.4049\/jimmunol.2100109","type":"journal-article","created":{"date-parts":[[2021,5,14]],"date-time":"2021-05-14T14:00:23Z","timestamp":1621000823000},"page":"2544-2551","source":"Crossref","is-referenced-by-count":24,"title":["The Protein Tyrosine Phosphatase SHP-1 (PTPN6) but Not CD45 (PTPRC) Is Essential for the Ligand-Mediated Regulation of CD22 in BCR-Ligated B Cells"],"prefix":"10.1093","volume":"206","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0284-9361","authenticated-orcid":false,"given":"Amin","family":"Alborzian Deh Sheikh","sequence":"first","affiliation":[{"name":"Department of Immunology, Medical Research Institute, Tokyo Medical and Dental University , Tokyo ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chizuru","family":"Akatsu","sequence":"additional","affiliation":[{"name":"Department of Immunology, Medical Research Institute, Tokyo Medical and Dental University , Tokyo ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4474-9086","authenticated-orcid":false,"given":"Hajjaj H M","family":"Abdu-Allah","sequence":"additional","affiliation":[{"name":"Faculty of Applied Biological Sciences, Gifu University , Gifu ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuki","family":"Suganuma","sequence":"additional","affiliation":[{"name":"Faculty of Applied Biological Sciences, Gifu University , Gifu ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akihiro","family":"Imamura","sequence":"additional","affiliation":[{"name":"Faculty of Applied Biological Sciences, Gifu University , Gifu ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiromune","family":"Ando","sequence":"additional","affiliation":[{"name":"Center for Highly Advanced Integration of Nano and Life Sciences, Gifu University , Gifu ,","place":["Japan"]},{"name":"Institute for Glyco-core Research, Gifu University , Gifu ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1689-9500","authenticated-orcid":false,"given":"Hiromu","family":"Takematsu","sequence":"additional","affiliation":[{"name":"Faculty of Medical Technology, Fujita Health University , Toyoake, Aichi ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8625-0929","authenticated-orcid":false,"given":"Hideharu","family":"Ishida","sequence":"additional","affiliation":[{"name":"Faculty of Applied Biological Sciences, Gifu University , Gifu ,","place":["Japan"]},{"name":"Center for Highly Advanced Integration of Nano and Life Sciences, Gifu University , Gifu ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0760-1258","authenticated-orcid":false,"given":"Takeshi","family":"Tsubata","sequence":"additional","affiliation":[{"name":"Department of Immunology, Medical Research Institute, Tokyo Medical and Dental University , Tokyo ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,6,1]]},"reference":[{"key":"2025030417503654700_r1","doi-asserted-by":"crossref","first-page":"2820","DOI":"10.3389\/fimmu.2018.02820","article-title":"B cell Siglecs-news on signaling and its interplay with ligand binding","volume":"9","author":"Meyer","year":"2018","journal-title":"Front. 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