title: TLR-mediated B cell defects and IFN-α in common variable immunodeficiency.
abstract: Common variable immune deficiency (CVID) B cells have impaired responses to TLR7 and TLR9 agonists including poor cell proliferation, loss of cytokine production, and failure to produce IgG or IgA. We show that TLR7- or 9-activated B cells from CVID subjects with >0.5% peripheral isotype-switched CD27(+) B cells (group 2) have increased mature Cγ1 and Cγ2 heavy-chain mRNA transcripts compared to subjects who have <0.5% isotype-switched cells (group 1). While TLR-stimulated CVID plasmacytoid dendritic cells for all subjects had impaired IFN-α production, TLR7 or TLR9 stimulation in the presence IFN-α normalized isotype-switched CD27(+) B cells, enhanced activation-induced cytidine deaminase mRNA, and significantly improved IgG production only for group 2 subjects. IFN-α also upregulated TLR7 and TLR9 mRNA expression comparable to normal levels in B cells of group 2 subjects, indicating that the loss of IFN-α could be a significant component of the B-cell defect for these subjects.
authors: Department of Medicine, Mount Sinai Medical Center, New York, NY 10029, USA.
authors: Joyce E
authors: JE
authors: Yu
authors: Li
authors: L
authors: Zhang
authors: Lin
authors: L
authors: Radigan
authors: Silvia
authors: S
authors: Sanchez-Ramon
authors: Charlotte
authors: C
authors: Cunningham-Rundles
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D017074:Common Variable Immunodeficiency / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D003564:Cytidine Deaminase / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism; D017578:Immunoglobulin Class Switching; D007074:Immunoglobulin G / Q000378:metabolism; D007142:Immunoglobulin gamma-Chains / Q000235:genetics; D016898:Interferon-alpha / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000276:immunology; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis; D051199:Toll-Like Receptor 7 / Q000235:genetics / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000378:metabolism; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007142:Immunoglobulin gamma-Chains; D016898:Interferon-alpha; D012333:RNA, Messenger; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase