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TLR-mediated B cell defects and IFN-α in common variable immunodeficiency.
J Clin Immunol. 2012 Feb; 32(1):50-60.JC

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+Show Affiliations

Department of Medicine, Mount Sinai Medical Center, New York, NY 10029, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22048980

Citation

Yu, Joyce E., et al. "TLR-mediated B Cell Defects and IFN-α in Common Variable Immunodeficiency." Journal of Clinical Immunology, vol. 32, no. 1, 2012, pp. 50-60.
Yu JE, Zhang L, Radigan L, et al. TLR-mediated B cell defects and IFN-α in common variable immunodeficiency. J Clin Immunol. 2012;32(1):50-60.
Yu, J. E., Zhang, L., Radigan, L., Sanchez-Ramon, S., & Cunningham-Rundles, C. (2012). TLR-mediated B cell defects and IFN-α in common variable immunodeficiency. Journal of Clinical Immunology, 32(1), 50-60. https://doi.org/10.1007/s10875-011-9602-y
Yu JE, et al. TLR-mediated B Cell Defects and IFN-α in Common Variable Immunodeficiency. J Clin Immunol. 2012;32(1):50-60. PubMed PMID: 22048980.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - TLR-mediated B cell defects and IFN-α in common variable immunodeficiency. AU - Yu,Joyce E, AU - Zhang,Li, AU - Radigan,Lin, AU - Sanchez-Ramon,Silvia, AU - Cunningham-Rundles,Charlotte, Y1 - 2011/11/03/ PY - 2011/07/29/received PY - 2011/09/20/accepted PY - 2011/11/4/entrez PY - 2011/11/4/pubmed PY - 2012/6/14/medline SP - 50 EP - 60 JF - Journal of clinical immunology JO - J. Clin. Immunol. VL - 32 IS - 1 N2 - 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. SN - 1573-2592 UR - https://www.unboundmedicine.com/medline/citation/22048980/TLR_mediated_B_cell_defects_and_IFN_α_in_common_variable_immunodeficiency_ L2 - https://doi.org/10.1007/s10875-011-9602-y DB - PRIME DP - Unbound Medicine ER -