Enhanced BAFF expression is negatively correlated with a suppressed isotype-switched memory B cell pool in CVID patients with complications

Abstract

Common variable immunodeficiency (CVID) is a primary immunodeficiency due to selected genetic defects. This syndrome is frequently associated with non-infectious complications such as interstitial lung disease, enteropathy, autoimmunity and malignancies, with lack of isotype-switched B cells. B cell–activating factor (BAFF) is one of the TNF family members important for IgA class switching and plasma cell survival. Excessive levels of BAFF are found in CVID patients. In this study, we investigated the correlation of BAFF levels with isotype-switched memory B cells. Serum BAFF levels in 70 CVID patients and 15 healthy controls were measured by ELISA. The percentages of isotype switched-memory B cells were measured by flow cytometry. The correlation between BAFF and isotype-switched memory B cells in CVID patients with and without complications were analyzed by Pearson’s correlation. The serum BAFF levels in all CVID patients were significantly higher than healthy controls (p<0.0001), whereas BAFF levels are higher in the group with non-infectious complications than the group without complications (p <0.005). In contrast, isotype-switched memory B cells were significantly lower in CVID patients than healthy controls (p <0.001). Furthermore, BAFF levels in all CVID patients and the group with complications were negatively correlated to isotype-switched memory B cells (p=0.012). Our data suggests that excessive BAFF expression in CVID patients with non-infectious complications may cause suppression of memory B cell switching. Alternatively exhaustive switching memory B cell pools in CVID patient may drive upregulation of BAFF, promoting the non-infectious complications. Future study to reveal the underlying mechanism is needed.