Journal Article

The p35 human invariant chain in transgenic mice restores mature B cells in the absence of endogenous CD74

Laetitia Genève, Catherine Ménard, Nathalie Labrecque and Jacques Thibodeau

in International Immunology Meeting Abstracts

Published on behalf of Japanese Society for Immunology

Volume 24, issue 10, pages 645-660
Published in print October 2012 |
Published online September 2012 | | DOI: https://dx.doi.org/10.1093/intimm/dxs066

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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-Ab . 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-Ab 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.

Keywords: invariant chain; Iip35; MHC; antigen presentation; transgenic mouse

Journal Article.  9425 words.  Illustrated.

Subjects: Immunology ; Biochemical Immunology

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