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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.

journal_name

J Clin Immunol

journal_title

Journal of clinical immunology

authors

Yu JE,Zhang L,Radigan L,Sanchez-Ramon S,Cunningham-Rundles C

doi

10.1007/s10875-011-9602-y

subject

Has Abstract

pub_date

2012-02-01 00:00:00

pages

50-60

issue

1

eissn

0271-9142

issn

1573-2592

journal_volume

32

pub_type

杂志文章

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