C T M Pereira1, D C Bichuetti-Silva1, N V F da Mota2, R Salomão2, M K C Brunialti2, B T Costa-Carvalho3. 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. 3. Department of Pediatrics, Federal University of Sao Paulo Medical School, 598, Botucatu Street, Vila Clementino, São Paulo, SP 04023-062, Brazil. Electronic address: beacarvalho@terra.com.br.
Abstract
BACKGROUND: Ataxia-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. METHODS: We 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. RESULTS: We 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. CONCLUSIONS: These findings revealed a disturbed B-cell homeostasis with unconventional maturation of B lymphocyte memory cells, which can explain the consequent impairment of humoral immunity.
BACKGROUND:Ataxia-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. METHODS: We 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. RESULTS: We 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. CONCLUSIONS: These findings revealed a disturbed B-cell homeostasis with unconventional maturation of B lymphocyte memory cells, which can explain the consequent impairment of humoral immunity.
Authors: Kofi A Mensah; Jeff W Chen; Jean-Nicolas Schickel; Isabelle Isnardi; Natsuko Yamakawa; Andrea Vega-Loza; Jennifer H Anolik; Richard A Gatti; Erwin W Gelfand; Ruth R Montgomery; Mark C Horowitz; Joe E Craft; Eric Meffre Journal: Sci Transl Med Date: 2019-11-20 Impact factor: 17.956
Authors: Rachel Warren; William Domm; Min Yee; Andrew Campbell; Jane Malone; Terry Wright; Margot Mayer-Pröschel; Michael A O'Reilly Journal: Am J Physiol Lung Cell Mol Physiol Date: 2019-09-11 Impact factor: 5.464