{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T05:39:13Z","timestamp":1790919553325,"version":"4.1.0"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2006,5,1]],"date-time":"2006-05-01T00:00:00Z","timestamp":1146441600000},"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":[[2006,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Protective host immune responses to anthrax infection in humans and animal models are characterized by the development of neutralizing Abs against the receptor-binding anthrax protective Ag (PA), which, together with the lethal factor (LF) protease, composes anthrax lethal toxin (LT). We now report that B cells, in turn, are targets for LT. Anthrax PA directly binds primary B cells, resulting in the LF-dependent cleavage of the MAPK kinases (MAPKKs) and disrupted signaling to downstream MAPK targets. Although not directly lethal to B cells, anthrax LT treatment causes severe B cell dysfunction, greatly reducing proliferative responses to IL-4-, anti-IgM-, and\/or anti-CD40 stimulation. Moreover, B cells treated with anthrax LT in vitro or isolated from mice treated with anthrax LT in vivo have a markedly diminished capacity to proliferate and produce IgM in response to TLR-2 and TLR-4 ligands. The suppressive effects of anthrax LT on B cell function occur at picomolar concentrations in vitro and at sublethal doses in vivo. These results indicate that anthrax LT directly inhibits the function of B cells in vitro and in vivo, revealing a potential mechanism through which the pathogen could bypass protective immune responses.<\/jats:p>","DOI":"10.4049\/jimmunol.176.10.6155","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T20:29:28Z","timestamp":1398025768000},"page":"6155-6161","source":"Crossref","is-referenced-by-count":64,"title":["Anthrax Lethal Toxin Has Direct and Potent Inhibitory Effects on B Cell Proliferation and Immunoglobulin Production"],"prefix":"10.1093","volume":"176","author":[{"given":"Hui","family":"Fang","sequence":"first","affiliation":[{"name":"Division of Monoclonal Antibodies, Office of Biotechnology Products, Office of Pharmaceutical Science, Center for Drug Evaluation and Research, U.S. Food and Drug Administration , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixin","family":"Xu","sequence":"additional","affiliation":[{"name":"Division of Monoclonal Antibodies, Office of Biotechnology Products, Office of Pharmaceutical Science, Center for Drug Evaluation and Research, U.S. Food and Drug Administration , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trina Y","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Monoclonal Antibodies, Office of Biotechnology Products, Office of Pharmaceutical Science, Center for Drug Evaluation and Research, U.S. Food and Drug Administration , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julianne M","family":"Cyr","sequence":"additional","affiliation":[{"name":"Division of Monoclonal Antibodies, Office of Biotechnology Products, Office of Pharmaceutical Science, Center for Drug Evaluation and Research, U.S. Food and Drug Administration , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M","family":"Frucht","sequence":"additional","affiliation":[{"name":"Division of Monoclonal Antibodies, Office of Biotechnology Products, Office of Pharmaceutical Science, Center for Drug Evaluation and Research, U.S. Food and Drug Administration , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2006,5,15]]},"reference":[{"key":"2026020211410529100_R1","first-page":"143","volume-title":"Curr. 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