Apolipoprotein-mediated lipid antigen presentation in B cells provides a pathway for innate help by NKT cells.
Natural killer T (NKT) cells are innate-like lymphocytes that recognize lipid antigens and have been shown to enhance B-cell activation and antibody production. B cells typically recruit T-cell help by presenting internalized antigens recognized by their surface antigen receptor. Here, we demonstrate a highly efficient means whereby human B cells present lipid antigens to NKT cells, capturing the antigen using apolipoprotein E (apoE) and the low-density lipoprotein receptor (LDL-R). ApoE dramatically enhances B-cell presentation of alpha-galactosylceramide (alphaGalCer), an exogenous CD1d presented antigen, inducing activation of NKT cells and the subsequent activation of B cells. B cells express the LDL-R on activation, and the activation of NKT cells by B cells is completely LDL-R dependent, as shown by blocking experiments and the complete lack of presentation when using apoE2, an isoform of apoE incapable of LDL-R binding. The dependence on apoE and the LDL-R is much more pronounced in B cells than we had previously seen in dendritic cells, which can apparently use alternate pathways of lipid antigen uptake. Thus, B cells use an apolipoprotein-mediated pathway of lipid antigen presentation, which constitutes a form of innate help for B cells by NKT cells.
Allan
Lenka L
LL
Department of Pathology and Laboratory Medicine, University of British Columbia, Child and Family Research Institute, Vancouver, Canada.
Hoefl
Katrin
K
Zheng
Dong-Jun
DJ
Chung
Brian K
BK
Kozak
Frederick K
FK
Tan
Rusung
R
van den Elzen
Peter
P
D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology*; D055610:Antigens, CD1d / Q000276:immunology*; D001057:Apolipoproteins E / Q000276:immunology / Q000378:metabolism*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D005434:Flow Cytometry; D005699:Galactosylceramides / Q000494:pharmacology; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D055611:Natural Killer T-Cells / Q000187:drug effects / Q000276:immunology*; D011973:Receptors, LDL / Q000378:metabolism; D015398:Signal Transduction
D055610:Antigens, CD1d; D001057:Apolipoproteins E; D005699:Galactosylceramides; D011973:Receptors, LDL; C493154:alpha-galactosylceramide