The effect of Casitas b-lineage lymphoma b on regulating T follicular helper in lupus nephritis.

Abstract

The purpose of this study was to investigate the effect of Casitas b-lineage lymphoma b (Cblb) on the regulation of T follicular helper (Tfh) in the development of lupus nephritis. The Tfh (CD4+CXCR5+PD-1+) cells in peripheral blood were analyzed by flow cytometry. Forty mice were divided into 4 groups (10/group), WT, lpr, Cblb-/- and lpr.Cblb-/-. Urine protein, serum creatinine, blood urea nitrogen (BUN), dsDNA, and antinuclear antibody (ANA) titer of mice were monitored once every four weeks. Peripheral blood mononuclear cells (PBMCs) from mice were collected to assess circulating Tfh. The expressions of Cblb in Tfh cells were regulated by transfecting siRNA and overexpression plasmid approach in vitro. The patients with lupus nephritis (LN) had abnormal renal clinical manifestations compared with healthy volunteers. The peripheral Tfh cells were increased and the expression of Cblb were downregulated in patients with LN (p<0.05). Both lpr mice and lpr.Cblb-/- mice had LN symptoms. LN symptoms were more serious in lpr.Cblb-/- mice compared with that in lpr mice (p<0.05). The number of Tfh cells in peripheral blood from lpr.Cblb-/- mice was significantly higher than that from lpr mice (p<0.05). Overexpression of Cblb in Tfh cells led to reduction of IgG expression, while the knockdown of Cblb in Tfh cells was accompanied by increased expression of immunoglobulin (IgG) (p<0.05). Cblb showed a negative regulatory effect on Tfh. The deletion of Cblb may be a key factor in progression of renal injury.