Regulatory B cells in CVID patients fail to suppress multifunctional IFN-gamma+TNF-alpha(+)CD4(+) T cells differentiation
Abstract
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-gamma+TNF-alpha(+) 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-gamma+TNF-alpha(+)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.