B-cell subsets imbalance and reduced expression of CD40 in ataxia-telangiectasia patients |
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Authors: | CTM Pereira DC Bichuetti-Silva NVF da Mota R Salomão MKC Brunialti BT Costa-Carvalho |
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Affiliation: | 1. Department of Pediatrics, Federal University of Sao Paulo Medical School, 598, Botucatu Street, Vila Clementino, São Paulo, SP 04023-062, Brazil;2. Division of Infectious Diseases, Federal University of Sao Paulo Medical School, 669, Pedro de Toledo Street, Vila Clementino, São Paulo, SP 04039-032, Brazil |
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Abstract: | BackgroundAtaxia-telangiectasia (AT) is a well-known primary immunodeficiency with recurrent sinopulmonary infections and variable abnormalities in both the humoral and cellular immune system. Dysfunctions in immunoglobulin production, reduced number of B cells, and B-cell receptor excision circles copies have been reported. We aimed to understand the immunological mechanisms involving the humoral compartment in AT patients by analysing peripheral blood B cells subsets, B-T lymphocyte cooperation through the expression of CD40 and CD40 ligand (CD40L), and cytokines involved in class-switch recombination production.MethodsWe compared the proportion of B-cell subsets, the expression of CD40/CD40L, and the plasma levels of IL-6 and IFN-γ of 18 AT patients and 15 healthy age-sex-matched controls using flow cytometry.ResultsWe found that some steps in peripheral B cell development were altered in AT with a pronounced reduction of cell-surface CD40 expression. The proportions of transitional and naïve-mature B cells were reduced, whereas CD21-low, natural effector memory, IgM-only memory, and IgG atypical memory B cells were present in a higher proportion.ConclusionsThese findings revealed a disturbed B-cell homeostasis with unconventional maturation of B lymphocyte memory cells, which can explain the consequent impairment of humoral immunity. |
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Keywords: | Ataxia-telangiectasia B cells CD40 CD40L IgM memory B cells Switched memory B cells CD21low |
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