title: Dendritic cells and follicular dendritic cells express a novel ligand for CD38 which influences their maturation and antibody responses.
abstract: CD38 is a cell surface molecule with ADP-ribosyl cyclase activity, which is predominantly expressed on lymphoid and myeloid cells. CD38 has a significant role in B-cell function as some anti-CD38 antibodies can deliver potent growth and differentiation signals, but the ligand that delivers this signal in mice is unknown. We used a chimeric protein of mouse CD38 and human immunogobulin G (IgG) (CD38-Ig) to identify a novel ligand for murine CD38 (CD38L) on networks of follicular dendritic cells (FDCs) as well as dendritic cells (DCs) in the spleen. Flow-cytometry found that all DC subsets expressed cytoplasmic CD38L but only fresh ex vivo CD11c+ CD11b- DCs had cell surface CD38L. Anti-CD38 antibody blocked the binding of CD38-Ig to CD38L, confirming the specificity of detection. CD38-Ig immuno-precipitated ligands of 66 and 130 kDa. Functional studies found that CD38-Ig along with anti-CD40 and anti-major histocompatibility complex (MHC) class II antibody provided maturation signals to DCs in vitro. When CD38-Ig was administered in vivo with antigen, IgG2a responses were significantly reduced, suggesting that B and T cells expressing CD38 may modulate the isotype of antibodies produced through interaction with CD38L on DCs. CD38-Ig also expanded FDC networks when administered in vivo. In conclusion, this study has identified a novel ligand for CD38 which has a role in functional interactions between lymphocytes and DCs or FDCs.
authors.affiliation: Queensland Institute of Medical Research, The Bancroft Center, Herston, Australia. michellW@qimr.edu.au
authors.forename: Michelle N
authors.initials: MN
authors.lastname: Wykes
authors.forename: Lynette
authors.initials: L
authors.lastname: Beattie
authors.forename: Gordon G
authors.initials: GG
authors.lastname: Macpherson
authors.forename: Derek N
authors.initials: DN
authors.lastname: Hart
mesh_terms: D036541:ADP-ribosyl Cyclase / Q000378:metabolism*; D051997:ADP-ribosyl Cyclase 1; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D020566:Dendritic Cells, Follicular / Q000276:immunology; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D005434:Flow Cytometry / Q000379:methods; D018858:Germinal Center / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D008024:Ligands; D008562:Membrane Glycoproteins; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000276:immunology
chemical_list: D015703:Antigens, CD; D007074:Immunoglobulin G; D008024:Ligands; D008562:Membrane Glycoproteins; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; C498155:Cd38 protein, mouse; D051997:ADP-ribosyl Cyclase 1