Apolipoprotein-mediated lipid antigen presentation in B cells provides a pathway for innate help by NKT cells

• Published in: Blood 2009-09, Vol.114 (12), p.2411-2416
• Main Authors: Allan, Lenka L., Hoefl, Katrin, Zheng, Dong-Jun, Chung, Brian K., Kozak, Frederick K., Tan, Rusung, van den Elzen, Peter
• Format: Article
• Language: English
• Subjects: Analysis of the immune response. Humoral and cellular immunity; Antigen Presentation - drug effects; Antigen Presentation - immunology; Antigens, CD1d - immunology; Apolipoproteins E - immunology; Apolipoproteins E - metabolism; B-Lymphocytes - drug effects; B-Lymphocytes - immunology; Biological and medical sciences; Cells, Cultured; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Galactosylceramides - pharmacology; Hematologic and hematopoietic diseases; Humans; Immunobiology; Lymphocyte Activation - drug effects; Medical sciences; Natural Killer T-Cells - drug effects; Natural Killer T-Cells - immunology; Organs and cells involved in the immune response; Receptors, LDL - metabolism; Signal Transduction
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2009-04-211417

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 (αGalCer), 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.