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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adolescent
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Adult
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Aged
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B-Lymphocytes / immunology*
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B-Lymphocytes / metabolism
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Common Variable Immunodeficiency / genetics
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Common Variable Immunodeficiency / immunology*
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Common Variable Immunodeficiency / metabolism
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Cytidine Deaminase / genetics
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Dendritic Cells / immunology
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Dendritic Cells / metabolism
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Humans
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Immunoglobulin A / metabolism
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Immunoglobulin Class Switching
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Immunoglobulin G / metabolism
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Immunoglobulin gamma-Chains / genetics
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Interferon-alpha / biosynthesis*
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Lymphocyte Activation / immunology
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Middle Aged
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RNA, Messenger / biosynthesis
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Toll-Like Receptor 7 / genetics
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Toll-Like Receptor 7 / metabolism
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Toll-Like Receptor 9 / genetics
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Toll-Like Receptor 9 / metabolism
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Toll-Like Receptors / genetics
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Toll-Like Receptors / metabolism*
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Young Adult
Substances
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Immunoglobulin A
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Immunoglobulin G
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Immunoglobulin gamma-Chains
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Interferon-alpha
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RNA, Messenger
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Toll-Like Receptor 7
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Toll-Like Receptor 9
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Toll-Like Receptors
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AICDA (activation-induced cytidine deaminase)
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Cytidine Deaminase