Regulatory B cells in CVID patients fail to suppress multifunctional IFN-γ+ TNF-α+ CD4+ T cells differentiation.
Common variable immunodeficiency (CVID) refers to primary hypogammaglobulinemia with unknown pathogenesis. Although there is evidence for intrinsic B cell defects in some CVID patient groups, various abnormalities in cytokine production by T cells in CVID patients are frequently observed. Here, we demonstrate a relationship in the production of pro-inflammatory Th1 cytokines and regulatory B cells producing IL-10 between CVID patients and healthy controls. We describe CD19(+)CD24(hi)CD38(hi)IL-10(+) regulatory B cells generated after T cell stimulation of human peripheral blood lymphocytes ex vivo are able to suppress IFN-γ(+)TNF-α(+) producing CD4(+) T cells. This process is impaired in CVID patients, who present with both low numbers of CD19(+)CD24(hi)CD38(hi)IL-10(+) B cells and increased numbers of IFN-γ(+)TNF-α(+)CD4(+) T cells. Disruption of the regulatory B cell response to T cell stimulation explains the excessive T cell activation regarded as an immunoregulatory abnormality that is a frequent finding in CVID patients.
['Vlkova|Marcela|M|', 'Ticha|Olga|O|', 'Nechvatalova|Jana|J|', 'Kalina|Tomas|T|', 'Litzman|Jiri|J|', 'Mauri|Claudia|C|', 'Blair|Paul A|PA|']
D000328:Adult D000368:Aged D000369:Aged, 80 and over D060151:B-Lymphocytes, Regulatory D015496:CD4-Positive T-Lymphocytes D002454:Cell Differentiation D017074:Common Variable Immunodeficiency D016207:Cytokines D005260:Female D005434:Flow Cytometry D006801:Humans D007371:Interferon-gamma D008213:Lymphocyte Activation D008297:Male D008875:Middle Aged D013601:T-Lymphocytes D014409:Tumor Necrosis Factor-alpha
B cell T cell Common variable immunodeficiency (CVID) Cytokine production Flow cytometry