TY - JOUR
T1 - The MHC class II cofactor HLA-DM interacts with Ig in B cells
AU - Macmillan, Henriette
AU - Strohman, Michael J.
AU - Ayyangar, Sashi
AU - Jiang, Wei
AU - Rajasekaran, Narendiran
AU - Spura, Armin
AU - Hessell, Ann J.
AU - Madec, Anne Marie
AU - Mellins, Elizabeth D.
N1 - Funding Information:
This work was supported by National Institutes of Health Grants AI095813 and AI075253 (both to E.D.M.), National Institutes of Health/National Center for Research Resources Clinical and Translational Science Award UL1 RR025744 (to H.M.), and the Lucile Packard Foundation for Children's Health. H.M. and M.J.S. were supported by National Institutes of Health Training Grant T32 AI07290 to the Stanford Interdisciplinary Program in Immunology.
Funding Information:
This work was supported by National Institutes of Health Grants AI095813 and AI075253 (both to E.D.M.), National Institutes of Health/National Center for Research Resources Clinical and Translational Science Award UL1 RR025744 (to H.M.), and the Lucile Packard Foundation for Children’s Health. H.M. and M.J.S. were supported by National Institutes of Health Training Grant T32 AI07290 to the Stanford Interdisciplinary Program in Immunology.
Publisher Copyright:
Copyright © 2014 by The American Association of Immunologists, Inc.
PY - 2014/9/15
Y1 - 2014/9/15
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.1400075
DO - 10.4049/jimmunol.1400075
M3 - Article
C2 - 25098292
AN - SCOPUS:84921689789
SN - 0022-1767
VL - 193
SP - 2641
EP - 2650
JO - Journal of Immunology
JF - Journal of Immunology
IS - 6
ER -