{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T05:22:04Z","timestamp":1790486524127,"version":"4.1.0"},"reference-count":68,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2015,10,1]],"date-time":"2015-10-01T00:00:00Z","timestamp":1443657600000},"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":[[2015,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The differentiation and survival of autoreactive B cells is normally limited by a variety of self-tolerance mechanisms, including clonal deletion, anergy, and clonal ignorance. The transcription factor c-ets-1 (encoded by the Ets1 gene) has B cell\u2013intrinsic roles in regulating formation of Ab-secreting cells by controlling the activity of Blimp1 and Pax5 and may be required for B cell tolerance to self-antigen. To test this, we crossed Ets1\u2212\/\u2212 mice to two different transgenic models of B cell self-reactivity, the anti\u2013hen egg lysozyme BCR transgenic strain and the AM14 rheumatoid factor transgenic strain. BCR transgenic Ets1\u2212\/\u2212 mice were subsequently crossed to mice either carrying or lacking relevant autoantigens. We found that B cells lacking c-ets-1 are generally hyperresponsive in terms of Ab secretion and form large numbers of Ab-secreting cells even in the absence of cognate Ags. When in the presence of cognate Ag, different responses were noted depending on the physical characteristics of the Ag. We found that clonal deletion of highly autoreactive B cells in the bone marrow was intact in the absence of c-ets-1. However, peripheral B cells lacking c-ets-1 failed to become tolerant in response to stimuli that normally induce B cell anergy or B cell clonal ignorance. Interestingly, high-affinity soluble self-antigen did cause B cells to adopt many of the classical features of anergic B cells, although such cells still secreted Ab. Therefore, maintenance of appropriate c-ets-1 levels is essential to prevent loss of self-tolerance in the B cell compartment.<\/jats:p>","DOI":"10.4049\/jimmunol.1500776","type":"journal-article","created":{"date-parts":[[2015,9,10]],"date-time":"2015-09-10T13:40:10Z","timestamp":1441892410000},"page":"3574-3583","source":"Crossref","is-referenced-by-count":33,"title":["Requirement for Transcription Factor <i>Ets1<\/i> in B Cell Tolerance to Self-Antigens"],"prefix":"10.1093","volume":"195","author":[{"given":"Lisa","family":"Russell","sequence":"first","affiliation":[{"name":"Department of Biochemistry, 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, State University of New York at Buffalo , Buffalo, NY 14203"},{"name":"Department of Laboratory Medicine, Yale University , New Haven, CT 06520"},{"name":"Department of Immunobiology, Yale University , New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime","family":"Cullen","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Yale University , New Haven, CT 06520"},{"name":"Department of Immunobiology, Yale University , New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, State University of New York at Buffalo , Buffalo, NY 14203"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J","family":"Shlomchik","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Pittsburgh School of Medicine , Pittsburgh, PA 15261"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7806-4352","authenticated-orcid":false,"given":"Lee Ann","family":"Garrett-Sinha","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, State University of New York at Buffalo , Buffalo, NY 14203"},{"name":"Department of Immunology, University of Pittsburgh School of Medicine , Pittsburgh, PA 15261"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,10,15]]},"reference":[{"key":"2025030704184235300_r1","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1126\/science.1086907","article-title":"Predominant autoantibody production by early human B cell precursors","volume":"301","author":"Wardemann","year":"2003","journal-title":"Science"},{"key":"2025030704184235300_r2","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1016\/j.immuni.2006.10.017","article-title":"Identification of anergic B cells within a wild-type repertoire","volume":"25","author":"Merrell","year":"2006","journal-title":"Immunity"},{"key":"2025030704184235300_r3","doi-asserted-by":"crossref","first-page":"4173","DOI":"10.4049\/jimmunol.140.12.4173","article-title":"Preferential autoantibody reactivity of the preimmune B cell repertoire in normal mice","volume":"140","author":"Souroujon","year":"1988","journal-title":"J. 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