{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T02:39:13Z","timestamp":1790735953257,"version":"4.1.0"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2016,5,1]],"date-time":"2016-05-01T00:00:00Z","timestamp":1462060800000},"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":[[2016,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Fc receptor\u2013like (FCRL) 5 is a novel IgG binding protein expressed on B cells, with the capacity to regulate Ag receptor signaling. We assessed FCRL5 expression on circulating B cells from healthy donors and found that FCRL5+ cells are most enriched among atypical CD21\u2212\/lo\/CD27\u2212 tissue-like memory (TLM) B cells, which are abnormally expanded in several autoimmune and infectious diseases. Using multicolor flow cytometry, FCRL5+ TLM cells were found to express more CD11c and several inhibitory receptors than did the FCRL5\u2212 TLM subset. The homing receptor profiles of the two TLM subsets shared features consistent with migration away from lymphoid tissues, but they also displayed distinct differences. Analysis of IgH V regions in single cells indicated that although both subsets are diverse, the FCRL5+ subset accumulated significantly more somatic mutations. Furthermore, the FCRL5+ subset had more switched isotype expression and more extensive proliferative history. Microarray analysis and quantitative RT-PCR demonstrated that the two TLM subsets possess distinct gene expression profiles, characterized by markedly different CD11c, SOX5, T-bet, and RTN4R expression, as well as differences in expression of inhibitory receptors. Functional analysis revealed that the FCRL5+ TLM subset responds poorly to multiple stimuli compared with the FCRL5\u2212 subset, as reflected by reduced calcium mobilization and blunted cell proliferation. We propose that the FCRL5+ TLM subset, but not the FCRL5\u2212 TLM subset, underwent Ag-driven development and is severely dysfunctional. The present study elucidates the heterogeneity of TLM B cells and provides the basis to dissect their roles in the pathogenesis of inflammatory and infectious diseases.<\/jats:p>","DOI":"10.4049\/jimmunol.1501027","type":"journal-article","created":{"date-parts":[[2016,4,14]],"date-time":"2016-04-14T00:10:06Z","timestamp":1460592606000},"page":"4064-4074","source":"Crossref","is-referenced-by-count":82,"title":["Fc Receptor\u2013like 5 Expression Distinguishes Two Distinct Subsets of Human Circulating Tissue\u2013like Memory B Cells"],"prefix":"10.1093","volume":"196","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5701-1518","authenticated-orcid":false,"given":"Huifang","family":"Li","sequence":"first","affiliation":[{"name":"Office of Biotechnology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration , Silver Spring, MD 20993"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Borrego","sequence":"additional","affiliation":[{"name":"Immunopathology Group, BioCruces Health Research Institute , 48903 Barakaldo ,","place":["Spain"]},{"name":"Ikerbasque, Basque Foundation for Science , 48013 Bilbao ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9156-5215","authenticated-orcid":false,"given":"Satoshi","family":"Nagata","sequence":"additional","affiliation":[{"name":"Center for Drug Design Research, National Institutes of Biomedical Innovation, Health and Nutrition , Ibaraki, Osaka 567-0085 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mate","family":"Tolnay","sequence":"additional","affiliation":[{"name":"Office of Biotechnology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration , Silver Spring, MD 20993"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2016,5,15]]},"reference":[{"key":"2025030702164480800_r1","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1038\/nri3802","article-title":"Memory B cells","volume":"15","author":"Kurosaki","year":"2015","journal-title":"Nat. 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