Regulatory B cells in CVID patients fail to suppress multifunctional IFN-γ+TNF-α+CD4+ T cells differentiation

- Human B reg cells are able to suppress production of IFN-γ+ and TNF-α+ by CD4+ T cells.
- We examine the role of B reg cells in CVID patients and healthy controls.
- Frequency of B reg cells is reduced in CVID patients.
- Production of multifunctional IFN-γ+ TNF-α+CD4+T cells is increased in CVID patients.
- Breg cells affect production of multifunctional IFN-γ+ TNF-α+CD4+T cells.

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.