Circulating Immature B Lymphocytes and Chronic ER Stress in CVID Patients

Abstract

Some CVID patients present large immature-looking B lymphocytes in the peripheral blood. Differentiation stages of B cells were qualified by multiparametric FCM and markers CD5, CD19, CD23, CD38, CD45, and FMC7. The analysis of 16 patients and 9 healthy donors revealed that all donors and 13 CVID patients had normal counts of prototypical mature B cells. However, 3 patients had increased numbers of immature and decreased numbers of mature B cells. Those immature cells were earlier stages normally restricted to lymphoid tissues. Analysis of the Unfolded Protein Response (UPR) revealed that B cells from one of these patients presented chronic ER stress, suggesting an inability to deal with physiological demands for protein folding. We identified a sub-group of CVID patients whose circulating immature B cells might be unable to produce Igs due to their immature state. The chronic ER stress found in one these patients interferes with the cell’s maturation program and lead to early apoptosis.