{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T19:25:21Z","timestamp":1790018721989,"version":"4.0.1"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2016,1,1]],"date-time":"2016-01-01T00:00:00Z","timestamp":1451606400000},"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":[[2016,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Marginal zone (MZ) and B1 B cells have the capacity to respond to foreign Ags more rapidly than conventional B cells, providing early immune responses to blood-borne pathogens. Ly9 (CD229, SLAMF3), a member of the signaling lymphocytic activation molecule family receptors, has been implicated in the development and function of innate T lymphocytes. In this article, we provide evidence that in Ly9-deficient mice splenic transitional 1, MZ, and B1a B cells are markedly expanded, whereas development of B lymphocytes in bone marrow is unaltered. Consistent with an increased number of these B cell subsets, we detected elevated levels of IgG3 natural Abs and a striking increase of T-independent type II Abs after immunization with 2,4,6-trinitrophenyl-Ficoll in the serum of Ly9-deficient mice. The notion that Ly9 could be a negative regulator of innate-like B cell responses was supported by the observation that administering an mAb directed against Ly9 to wild-type mice selectively eliminated splenic MZ B cells and significantly reduced the numbers of B1 and transitional 1 B cells. In addition, Ly9 mAb dramatically diminished in vivo humoral responses and caused a selective downregulation of the CD19\/CD21\/CD81 complex on B cells and concomitantly an impaired B cell survival and activation in an Fc-independent manner. We conclude that altered signaling caused by the absence of Ly9 or induced by anti-Ly9 may negatively regulate development and function of innate-like B cells by modulating B cell activation thresholds. The results suggest that Ly9 could serve as a novel target for the treatment of B cell\u2013related diseases.<\/jats:p>","DOI":"10.4049\/jimmunol.1501266","type":"journal-article","created":{"date-parts":[[2015,12,15]],"date-time":"2015-12-15T04:24:08Z","timestamp":1450153448000},"page":"726-737","source":"Crossref","is-referenced-by-count":20,"title":["Targeting of Ly9 (CD229) Disrupts Marginal Zone and B1 B Cell Homeostasis and Antibody Responses"],"prefix":"10.1093","volume":"196","author":[{"given":"Marta","family":"Cuenca","sequence":"first","affiliation":[{"name":"Immunology Unit, Department of Cell Biology, Immunology and Neurosciences, Medical School, University of Barcelona , Barcelona 08036 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Romero","sequence":"additional","affiliation":[{"name":"Immunology Unit, Department of Cell Biology, Immunology and Neurosciences, Medical School, University of Barcelona , Barcelona 08036 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"Sintes","sequence":"additional","affiliation":[{"name":"Immunology Unit, Department of Cell Biology, Immunology and Neurosciences, Medical School, University of Barcelona , Barcelona 08036 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cox","family":"Terhorst","sequence":"additional","affiliation":[{"name":"Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School , Boston, MA 02215"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8410-252X","authenticated-orcid":false,"given":"Pablo","family":"Engel","sequence":"additional","affiliation":[{"name":"Immunology Unit, Department of Cell Biology, Immunology and Neurosciences, Medical School, University of Barcelona , Barcelona 08036 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2016,1,15]]},"reference":[{"key":"2025030702121001900_r1","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. 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