Phenotypic and Functional Analysis of T Follicular Cells in Common Variable Immunodeficiency.

INTRODUCTION: One of the most frequent abnormalities of B cells in common variable immunodeficiency (CVID) is reduced number of class-switched memory B cells, suggesting an impaired germinal center response. Therefore, due to its pivotal role in regulating the development of humoral immunity, the objective of this study was to evaluate the role of circulating T follicular helper (cTFH) and circulating T follicular regulatory (cTFR) cells in the pathogenesis of CVID.

METHODS: cTFH and cTFR cells from CVID patients and healthy subjects were phenotypically characterized by flow cytometry. cTFH and memory B cells from CVID patients and healthy subjects were isolated and cocultured.

RESULTS: Our results showed a reduced proportion of cTFH17 cells in patients with CVID and an increased ratio of cTFH/cTFR cells in CVID patients with autoimmune diseases. Furthermore, the proportion of IL-21-producing cTFH cells was directly related to the proportion of CD27+ IgD- B cells. Interestingly, coculture assay showed that CVID-derived cTFH cells are able to help memory B cells from healthy controls to produce immunoglobulins.

CONCLUSIONS: The proportions of cTFH17 and cTFR cells are altered in CVID patients; however, the cTFH function in assisting B cells to produce antibodies in vitro is preserved.