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As in other <jats:styled-content style=\"fixed-case\">APC<\/jats:styled-content>s, antigen presentation by B cells involves antigen internalization, antigen processing, and peptide loading onto <jats:styled-content style=\"fixed-case\">MHC<\/jats:styled-content> molecules. However, while the mechanism of antigen processing has been studied extensively in other <jats:styled-content style=\"fixed-case\">APC<\/jats:styled-content>s, this pathway remains elusive in B cells. The aim of this study was to investigate the <jats:styled-content style=\"fixed-case\">MHC<\/jats:styled-content> class <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> processing pathway in <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>40\u2010activated B cells (<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>40Bs), as a model for activated, antigen\u2010presenting B cells. Using <jats:styled-content style=\"fixed-case\">CMV<\/jats:styled-content> pp65 as a model antigen, we evaluated processing and presentation of the <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4\u00a0+\u00a0T\u2010cell epitope 509\u2010523 (K509) by human <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>40Bs in <jats:styled-content style=\"fixed-case\">ELISPOT<\/jats:styled-content> assays. As expected, stimulation of specific <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4\u00a0+\u00a0T\u2010cell clones was attenuated after pretreatment of <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>40Bs with inhibitors of classic class <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> pathway components. However, proteasome inhibitors such as epoxomicin limited antigen presentation as well. This suggests that the antigen is processed in a non\u2010classical, cytosolic <jats:styled-content style=\"fixed-case\">MHC<\/jats:styled-content> class <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> pathway. Further experiments with truncated protein variants revealed involvement of the proteasome in processing of the N and C extensions of the epitope. Access to the cytosol was shown to be size dependent. Epoxomicin sensitivity exclusively in <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>40B cells, but not in dendritic cells, suggests a novel processing mechanism unique to this <jats:styled-content style=\"fixed-case\">APC<\/jats:styled-content>. Our data suggest that B cells process antigen using a distinct, non\u2010classical class <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> pathway.<\/jats:p>","DOI":"10.1111\/ejh.12699","type":"journal-article","created":{"date-parts":[[2015,11,12]],"date-time":"2015-11-12T04:08:41Z","timestamp":1447301321000},"page":"166-174","source":"Crossref","is-referenced-by-count":14,"title":["Processing and <scp>MHC<\/scp> class <scp>II<\/scp> presentation of exogenous soluble antigen involving a proteasome\u2010dependent cytosolic pathway in <scp>CD<\/scp>40\u2010activated B cells"],"prefix":"10.1111","volume":"97","author":[{"given":"Hans Jiro","family":"Becker","sequence":"first","affiliation":[{"name":"Cologne Interventional Immunology Cologne University Hospital Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eisei","family":"Kondo","sequence":"additional","affiliation":[{"name":"Department of General Medicine Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Shimabukuro\u2010Vornhagen","sequence":"additional","affiliation":[{"name":"Cologne Interventional Immunology Cologne University Hospital Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Theurich","sequence":"additional","affiliation":[{"name":"Cologne Interventional Immunology Cologne University Hospital Cologne Germany"},{"name":"Max Planck Institute for Metabolism Research Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S.","family":"von Bergwelt\u2010Baildon","sequence":"additional","affiliation":[{"name":"Cologne Interventional Immunology Cologne University Hospital Cologne 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