title: CD40 mediates downregulation of CD32B on specific memory B cell populations in rheumatoid arthritis.
abstract: Altered B cell function is important in the pathogenesis of rheumatoid arthritis (RA). In this report, we show that patients with active RA have an increased frequency of CD32B low/neg cells in the CD27(+)IgD(-) memory B cell subset and that these changes are associated with phenotypic and functional B cell activation. Studies using PBMCs from healthy donors revealed that downregulation of CD32B on B cells is mediated by CD40-CD40L interactions and is potentiated by IL-4 and inhibited by both IL-10 and IL-21. These findings appear physiologically relevant because CD4 T cell expression of CD40L correlated with the frequency of CD32B low/neg cells in the CD27(+)IgD(-) memory B subset in patients with RA. Our data support a model in which high levels of CD40L, present on circulating T cells in patients with RA, causes B cell activation and CD32B downregulation, resulting in secondary protection of memory B cells from CD32B-mediated cell death.
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, University of Maryland, Baltimore, MD 21201, USA.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Zhang
authors.forename: Erin
authors.initials: E
authors.lastname: Burch
authors.forename: Ling
authors.initials: L
authors.lastname: Cai
authors.forename: Edward
authors.initials: E
authors.lastname: So
authors.forename: Fleesie
authors.initials: F
authors.lastname: Hubbard
authors.forename: Eric L
authors.initials: EL
authors.lastname: Matteson
authors.forename: Scott E
authors.initials: SE
authors.lastname: Strome
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D019013:CD40 Antigens / Q000276:immunology* / Q000378:metabolism; D023201:CD40 Ligand / Q000276:immunology / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D017452:Receptors, IgG / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D019013:CD40 Antigens; C080571:Fc gamma receptor IIB; D017452:Receptors, IgG; D023201:CD40 Ligand