The MHC class II cofactor HLA-DM interacts with Ig in B cells

Henriette Macmillan, Michael J. Strohman, Sashi Ayyangar, Wei Jiang, Narendiran Rajasekaran, Armin Spura, Ann J. Hessell, Anne Marie Madec, Elizabeth D. Mellins

    Research output: Contribution to journalArticle

    10 Scopus citations

    Abstract

    B cells internalize extracellular Ag into endosomes using the Ig component of the BCR. In endosomes, Ag-derived peptides are loaded onto MHC class II proteins. How these pathways intersect remains unclear. We find that HLA-DM (DM), a catalyst for MHC class II peptide loading, coprecipitates with Ig in lysates from human tonsillar B cells and B cell lines. The molecules in the Ig/DM complexes have mature glycans, and the complexes colocalize with endosomal markers in intact cells. A larger fraction of Ig precipitates with DM after BCR crosslinking, implying that complexes can form when DM meets endocytosed Ig. In vitro, in the endosomal pH range, soluble DM directly binds the Ig Fab domain and increases levels of free Ag released from immune complexes. Taken together, these results argue that DM and Ig intersect in the endocytic pathway of B cells with potential functional consequences.

    Original languageEnglish (US)
    Pages (from-to)2641-2650
    Number of pages10
    JournalJournal of Immunology
    Volume193
    Issue number6
    DOIs
    StatePublished - Sep 15 2014

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology

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  • Cite this

    Macmillan, H., Strohman, M. J., Ayyangar, S., Jiang, W., Rajasekaran, N., Spura, A., Hessell, A. J., Madec, A. M., & Mellins, E. D. (2014). The MHC class II cofactor HLA-DM interacts with Ig in B cells. Journal of Immunology, 193(6), 2641-2650. https://doi.org/10.4049/jimmunol.1400075