{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:39:54Z","timestamp":1791247194957,"version":"4.1.0"},"reference-count":78,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2006,10,1]],"date-time":"2006-10-01T00:00:00Z","timestamp":1159660800000},"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":[[2006,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Differentiation of B cells into plasma cells represents a critical immunoregulatory checkpoint where neutralizing Abs against infectious agents must be selected whereas self-reactive Abs are suppressed. Bacterial LPS is a uniquely potent bacterial immunogen that can bypass self-tolerance within the T cell repertoire. We show here that during LPS-induced plasma cell differentiation, the ERK intracellular signaling pathway serves as a pivotal switch integrating opposing inputs from Ag via BCR and from the two best characterized B cell differentiation factors made by T cells, IL-2 and IL-5. Continuous Ag receptor signaling through the RAS\/MEK\/ERK pathway, as occurs in self-reactive B cells, inhibits LPS induction of Blimp-1 and the plasma cell differentiation program. Differentiation resumes after a transient pulse of Ag-ERK signaling, or upon inactivation of ERK by IL-2 and IL-5 through induction of dual-specificity phosphatase 5 (Dusp5). The architecture of this molecular switch provides a framework for understanding the specificity of antibacterial Ab responses and resistance to bacterially induced autoimmune diseases such as Guillain-Barre\u0301 syndrome.<\/jats:p>","DOI":"10.4049\/jimmunol.177.8.5337","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:20:27Z","timestamp":1397848827000},"page":"5337-5346","source":"Crossref","is-referenced-by-count":76,"title":["ERK Signaling Is a Molecular Switch Integrating Opposing Inputs from B Cell Receptor and T Cell Cytokines to Control TLR4-Driven Plasma Cell Differentiation"],"prefix":"10.1093","volume":"177","author":[{"given":"Lixin","family":"Rui","sequence":"first","affiliation":[{"name":"Australian Cancer Research Foundation Genetics Laboratory and Medical Genome Centre, John Curtin School of Medical Research, Australian Phenomics Facility, Australian National University , Canberra ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James I","family":"Healy","sequence":"additional","affiliation":[{"name":"Australian Cancer Research Foundation Genetics Laboratory and Medical Genome Centre, John Curtin School of Medical Research, Australian Phenomics Facility, Australian National University , Canberra ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Blasioli","sequence":"additional","affiliation":[{"name":"Australian Cancer Research Foundation Genetics Laboratory and Medical Genome Centre, John Curtin School of Medical Research, Australian Phenomics Facility, Australian National University , Canberra ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher C","family":"Goodnow","sequence":"additional","affiliation":[{"name":"Australian Cancer Research Foundation Genetics Laboratory and Medical Genome Centre, John Curtin School of Medical Research, Australian Phenomics Facility, Australian National University , Canberra ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2006,10,15]]},"reference":[{"key":"2026020211125643700_R1","first-page":"645","volume-title":"Annu. 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