title: CD1d and CD1c expression in human B cells is regulated by activation and retinoic acid receptor signaling.
abstract: B cell activation and Ab production in response to protein Ags requires presentation of peptides for recruitment of T cell help. We and others have recently demonstrated that B cells can also acquire innate help by presenting lipid Ags via CD1d to NKT cells. Given the newfound contribution of NKT cells to humoral immunity, we sought to identify the pathways that regulate CD1 molecule expression in human B cells. We show that ex vivo, activated and memory B cells expressed lower levels of CD1d compared with resting, naive, and marginal zone-like B cells. In vitro, CD1d was downregulated by all forms of B cell activation, leaving a narrow temporal window in which B cells could activate NKT cells. CD1c expression and function also decreased following activation by CD40L alone, whereas activation via the BCR significantly upregulated CD1c, particularly on marginal zone-like B cells. We found that the CD40L-induced downregulation of CD1d and CD1c correlated with diminished expression of retinoic acid receptor α (RARα) response genes, an effect that was reversed by RARα agonists. However, BCR-induced upregulation of CD1c was independent of the RAR pathway. Our findings that both CD1d and CD1c are upregulated by RARα signaling in human B cells is distinct from effects reported in dendritic cells, in which CD1c is inversely downregulated. One functional consequence of CD1d upregulation by retinoic acid was NKT cell cytotoxicity toward B cells. These results are central to our understanding of how CD1-restricted T cells may control humoral immunity.
authors: Department of Pathology and Laboratory Medicine, University of British Columbia, Child and Family Research Institute, Vancouver, British Columbia V5Z 4H4, Canada.
authors: Lenka L
authors: LL
authors: Allan
authors: Annelein M
authors: AM
authors: Stax
authors: Dong-Jun
authors: DJ
authors: Zheng
authors: Brian K
authors: BK
authors: Chung
authors: Fred K
authors: FK
authors: Kozak
authors: Rusung
authors: R
authors: Tan
authors: Peter
authors: P
authors: van den Elzen
mesh_terms: D017951:Antigen Presentation / Q000276:immunology; D018949:Antigens, CD1 / Q000096:biosynthesis* / Q000276:immunology; D055610:Antigens, CD1d / Q000096:biosynthesis* / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002469:Cell Separation; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006023:Glycoproteins / Q000096:biosynthesis* / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D055611:Natural Killer T-Cells / Q000276:immunology; D018168:Receptors, Retinoic Acid / Q000276:immunology / Q000378:metabolism*; D000072482:Retinoic Acid Receptor alpha; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D018949:Antigens, CD1; D055610:Antigens, CD1d; C437944:CD1C protein, human; C526877:CD1D protein, human; D006023:Glycoproteins; C000607071:RARA protein, human; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha