Regulatory B cells in CVID patients fail to suppress multifunctional IFN-γ+TNF-α+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+CD24hiCD38hiIL-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+CD24hiCD38hiIL-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.