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The p35 human invariant chain in transgenic mice restores mature B cells in the absence of endogenous CD74.
MedLine Citation:
PMID:  22966065     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The invariant chain (Ii; CD74) has pleiotropic functions and Ii-deficient mice show defects in MHC class II (MHC II) transport and B cell maturation. In humans, but not in mice, a minor Iip35 isoform of unknown function includes an endoplasmic reticulum-retention motif that is masked upon binding of MHC II molecules. To gain further insight into the roles of Ii in B cell homeostasis, we generated Iip35 transgenic mice (Tgp35) and bred these with mice deficient for Ii (Tgp35/mIiKO). Iip35 was shown to compete with mIi for the binding to I-A(b) . In addition, classical endosomal degradation products (p20/p10) and the class II-associated invariant chain peptide (CLIP) fragment were detected. Moreover, Iip35 favored the formation of compact peptide-MHC II complexes in the Tgp35/mIiKO mice. I-A(b) levels were restored at the plasma membrane of mature B cells but Iip35 affected the fine conformation of MHC II molecules as judged by the increased reactivity of the AF6-120.1 antibody in permeabilized cells. However, the human Iip35 cannot fully replace the endogenous Ii. Indeed, most immature B cells in the bone marrow and spleen of transgenic mice had reduced surface expression of MHC II molecules, demonstrating a dominant-negative effect of Iip35 in Tgp35 mice. Interestingly, while maturation to follicular B cells was normal, Iip35 expression appeared to reduce the proportions of marginal zone B cells. These results emphasize the importance of Ii in B cell homeostasis and suggest that Iip35 could have regulatory functions.
Authors:
Laetitia Genève; Catherine Ménard; Nathalie Labrecque; Jacques Thibodeau
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-9-10
Journal Detail:
Title:  International immunology     Volume:  -     ISSN:  1460-2377     ISO Abbreviation:  Int. Immunol.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-9-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8916182     Medline TA:  Int Immunol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Laboratoire d'Immunologie Moléculaire, Département de Microbiologie et Immunologie, Université de Montréal, Montréal, Québec H3T1J4, Canada.
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