{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T14:37:18Z","timestamp":1790433438746,"version":"4.1.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2017,7,1]],"date-time":"2017-07-01T00:00:00Z","timestamp":1498867200000},"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":[[2017,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The invariant chain (CD74) mediates assembly and targeting of MHC class II (MHCII) complexes. In endosomes, CD74 undergoes sequential degradation by different proteases, including cathepsin S (CatS) and the intramembrane protease signal peptide peptidase-like 2a (SPPL2a). In their absence, CD74 N-terminal fragments (NTFs) accumulate. In SPPL2a\u2212\/\u2212 B cells, such an NTF impairs endosomal trafficking and BCR signal transduction. In mice, this leads to a loss of splenic B cells beyond the transitional stage 1. To gain insight into CD74 determinants and the role of MHCII, we compared B cells from CatS\u2212\/\u2212, SPPL2a\u2212\/\u2212, and SPPL2a-MHCII double-deficient mice. We assessed differentiation of B cells in bone marrow and spleen and analyzed their endosomal morphology, BCR expression, and signal transduction. We demonstrate that MHCII is dispensable for the B cell phenotype of SPPL2a\u2212\/\u2212 mice, further supporting a CD74-intrinsic effect. Despite significant vacuolization of endosomal compartments similar to SPPL2a\u2212\/\u2212 B cells, CatS\u2212\/\u2212 traditional stage 1 B cells show unimpaired degradation of endocytic cargo, have intact BCR signaling, and do not exhibit any relevant defects in maturation. This could indicate that CD74 NTF\u2013induced structural changes of endosomes are not directly involved in these processes. We further found that the block of CD74 degradation in CatS\u2212\/\u2212 B cells is incomplete, so that NTF levels are significantly lower than in SPPL2a\u2212\/\u2212 B cells. This suggests a dose dependency and threshold for the CD74 NTF\u2013associated impairment of B cell signaling and maturation. In addition, different functional properties of the longer, MHCII-bound CD74 NTF could contribute to the milder phenotype of CatS\u2212\/\u2212 B cells.<\/jats:p>","DOI":"10.4049\/jimmunol.1601533","type":"journal-article","created":{"date-parts":[[2017,5,27]],"date-time":"2017-05-27T00:50:25Z","timestamp":1495846225000},"page":"172-185","source":"Crossref","is-referenced-by-count":14,"title":["The Influence of MHC Class II on B Cell Defects Induced by Invariant Chain\/CD74 N-Terminal Fragments"],"prefix":"10.1093","volume":"199","author":[{"given":"Janna","family":"Schneppenheim","sequence":"first","affiliation":[{"name":"Biochemical Institute, Christian-Albrechts-University of Kiel , D-24118 Kiel,","place":["Germany"]},{"name":"Institute of Anatomy, Christian-Albrechts-University of Kiel , D-24118 Kiel,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann-Christine","family":"Loock","sequence":"additional","affiliation":[{"name":"Biochemical Institute, Christian-Albrechts-University of Kiel , D-24118 Kiel,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susann","family":"H\u00fcttl","sequence":"additional","affiliation":[{"name":"Biochemical Institute, Christian-Albrechts-University of Kiel , D-24118 Kiel,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"Schweizer","sequence":"additional","affiliation":[{"name":"Center for Molecular Neurobiology, University Hospital Hamburg-Eppendorf , D-20246 Hamburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renate","family":"L\u00fcllmann-Rauch","sequence":"additional","affiliation":[{"name":"Institute of Anatomy, Christian-Albrechts-University of Kiel , D-24118 Kiel,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Heinrich","family":"Oberg","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Christian-Albrechts-University of Kiel , D-24105 Kiel,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Arnold","sequence":"additional","affiliation":[{"name":"Institute of Anatomy, Christian-Albrechts-University of Kiel , D-24118 Kiel,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5927-9761","authenticated-orcid":false,"given":"Christian H K","family":"Lehmann","sequence":"additional","affiliation":[{"name":"Laboratory of Dendritic Cell Biology, Department of Dermatology, Friedrich-Alexander University Erlangen-N\u00fcrnberg, University Hospital Erlangen , D-91052 Erlangen,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9358-134X","authenticated-orcid":false,"given":"Diana","family":"Dudziak","sequence":"additional","affiliation":[{"name":"Laboratory of Dendritic Cell Biology, Department of Dermatology, Friedrich-Alexander University Erlangen-N\u00fcrnberg, University Hospital Erlangen , D-91052 Erlangen,","place":["Germany"]},{"name":"Medical Immunology Campus Erlangen , D-91054 Erlangen,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dieter","family":"Kabelitz","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Christian-Albrechts-University of Kiel , D-24105 Kiel,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph","family":"Lucius","sequence":"additional","affiliation":[{"name":"Institute of Anatomy, Christian-Albrechts-University of Kiel , D-24118 Kiel,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana-Maria","family":"Lennon-Dum\u00e9nil","sequence":"additional","affiliation":[{"name":"INSERM\u2014U932 Immunit\u00e9 et Cancer, Institut Curie, Universit\u00e9 Paris Sciences et Lettres , 75248 Paris Cedex 05,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Saftig","sequence":"additional","affiliation":[{"name":"Biochemical Institute, Christian-Albrechts-University of Kiel , D-24118 Kiel,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Schr\u00f6der","sequence":"additional","affiliation":[{"name":"Biochemical Institute, Christian-Albrechts-University of Kiel , D-24118 Kiel,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,7,1]]},"reference":[{"issue":"6 Pt. 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