X chromosome gene Ddx3x is involved in B-cell development

Abstract

Abstract Ddx3x, located on the X chromosome, belongs to the DEAD box RNA helicase family. Ddx3x is previously implicated in RNA metabolism, cell cycle control, apoptosis, tumorigeneses and viral infections. In the process of exploring the role of ddx3x in the female predominance of systemic lupus erythematosus, we found abnormalities in B-cell development within conditional ddx3x-deficient mice. Breeding of ddx3x-floxed mice with Vav1-Cre mice led to deletion of ddx3x in hematopoietic cells (Vav1ddx3x). Ddx3x expression was reduced 80% in the bone marrow (BM) of Vav1ddx3x mice. Hematopoietic deficiency of ddx3x is associated with a reduced proportion and absolute number of B cells, starting at the small pre-B cell stage, and then subsequently immature B cells and mature B cells in bone marrow, relative to wild-type mice. In spleen, the frequency and number of follicular B cells (FOB) were significantly decreased whereas the numbers of marginal zone, germinal center and plasma-blast B cells were sustained. Mixed Vav1ddx3x and wild-type bone marrow chimera mice demonstrated a B-cell intrinsic effect. Surprisingly, despite fewer B cells in the BM and spleen, serum IgM, IgA and IgG titers were elevated in Vav1ddx3x mice, suggesting ddx3x may affect B-cell function as well. In conclusion, we showed that ddx3x deficiency affects B-cell development resulting in a loss of B cells in bone marrow and the periphery and an increase in serum immunoglobulin levels.