{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T22:02:03Z","timestamp":1790373723328,"version":"4.1.0"},"reference-count":56,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"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":[[2015,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Tight control of B cell differentiation into plasma cells (PCs) is critical for proper immune responses and the prevention of autoimmunity. The Ets1 transcription factor acts in B cells to prevent PC differentiation. Ets1\u2212\/\u2212 mice accumulate PCs and produce autoantibodies. Ets1 expression is downregulated upon B cell activation through the BCR and TLRs and is maintained by the inhibitory signaling pathway mediated by Lyn, CD22 and SiglecG, and SHP-1. In the absence of these inhibitory components, Ets1 levels are reduced in B cells in a Btk-dependent manner. This leads to increased PCs, autoantibodies, and an autoimmune phenotype similar to that of Ets1\u2212\/\u2212 mice. Defects in inhibitory signaling molecules, including Lyn and Ets1, are associated with human lupus, although the effects are more subtle than the complete deficiency that occurs in knockout mice. In this study, we explore the effect of partial disruption of the Lyn\/Ets1 pathway on B cell tolerance and find that Lyn+\/\u2212Ets1+\/\u2212 mice demonstrate greater and earlier production of IgM, but not IgG, autoantibodies compared with Lyn+\/\u2212 or Ets1+\/\u2212 mice. We also show that Btk-dependent downregulation of Ets1 is important for normal PC homeostasis when inhibitory signaling is intact. Ets1 deficiency restores the decrease in steady state PCs and Ab levels observed in Btk\u2212\/\u2212 mice. Thus, depending on the balance of activating and inhibitory signals to Ets1, there is a continuum of effects on autoantibody production and PC maintenance. This ranges from full-blown autoimmunity with complete loss of Ets1-maintaining signals to reduced PC and Ab levels with impaired Ets1 downregulation.<\/jats:p>","DOI":"10.4049\/jimmunol.1500165","type":"journal-article","created":{"date-parts":[[2015,7,25]],"date-time":"2015-07-25T03:05:08Z","timestamp":1437793508000},"page":"1955-1963","source":"Crossref","is-referenced-by-count":21,"title":["Genetic Interaction between Lyn, Ets1, and Btk in the Control of Antibody Levels"],"prefix":"10.1093","volume":"195","author":[{"given":"Jessica","family":"Mayeux","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, University of Texas Southwestern Medical Center , Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Skaug","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Texas Southwestern Medical Center , Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Center of Excellence in Bioinformatics and Life Sciences, State University of New York at Buffalo , Buffalo, NY 14203"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa M","family":"Russell","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Center of Excellence in Bioinformatics and Life Sciences, State University of New York at Buffalo , Buffalo, NY 14203"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinu","family":"John","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Center of Excellence in Bioinformatics and Life Sciences, State University of New York at Buffalo , Buffalo, NY 14203"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prontip","family":"Saelee","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Center of Excellence in Bioinformatics and Life Sciences, State University of New York at Buffalo , Buffalo, NY 14203"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hansaa","family":"Abbasi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Texas Southwestern Medical Center , Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan-Zhen","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Texas Southwestern Medical Center , Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee Ann","family":"Garrett-Sinha","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Center of Excellence in Bioinformatics and Life Sciences, State University of New York at Buffalo , Buffalo, NY 14203"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne B","family":"Satterthwaite","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Texas Southwestern Medical Center , Dallas, TX 75390"},{"name":"Department of Immunology, University of Texas Southwestern Medical Center , Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,9,1]]},"reference":[{"key":"2025030704080556900_r1","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1128\/MCB.00612-13","article-title":"Transcription factor Ets1, but not the closely related factor Ets2, inhibits antibody-secreting cell differentiation","volume":"34","author":"John","year":"2014","journal-title":"Mol. Cell. Biol."},{"key":"2025030704080556900_r2","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1074\/jbc.M705262200","article-title":"Ets-1 regulates plasma cell differentiation by interfering with the activity of the transcription factor Blimp-1","volume":"283","author":"John","year":"2008","journal-title":"J. Biol. Chem."},{"key":"2025030704080556900_r3","doi-asserted-by":"crossref","first-page":"3375","DOI":"10.1007\/s00018-012-1243-7","article-title":"Review of Ets1 structure, function, and roles in immunity","volume":"70","author":"Garrett-Sinha","year":"2013","journal-title":"Cell. Mol. Life Sci."},{"key":"2025030704080556900_r4","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1093\/intimm\/dxh295","article-title":"Ets-1 deficiency leads to altered B cell differentiation, hyperresponsiveness to TLR9 and autoimmune disease","volume":"17","author":"Wang","year":"2005","journal-title":"Int. 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