Circulating follicular T helper cells are possibly associated with low levels of serum immunoglobulin G due to impaired immunoglobulin class-switch recombination of B cells in children with primary nephrotic syndrome.
Clinically, most patients with primary nephrotic syndrome (PNS) have low serum IgG levels, which is an important factor in infection and in PNS relapse.To some extent, the mechanisms involved remain largely unknown. Here, we aimed to investigate the pathogenesis of the decreased IgG levels in PNS. Peripheral blood was collected from patients with PNS and closely age- and sex-matched healthy individuals. The frequency, phenotype and molecular function of different circulating B cell and T follicular helper cell (TFH) subsets were examined by flow cytometry. The function of the CD40/CD40 L interaction in immunoglobulin class-switch recombination (CSR) was evaluated by assessing the induction of activation-induced deaminase (AID) expression with CD40 L stimulation. We revealed an increase in the levels of circulating total plasmablasts, plasma cells and mature-naive B cells and a decrease in the levels of germinal centre-like B cells and CD19+IgG+ B cells in PNS. In addition, although the expression of CD86 on the surface of B cells and the expression of the inducible costimulator (ICOS) on the surface of TFH cells both were increased, the expression of CD40 L on the surface of TFH cells was decreased. Moreover, upon stimulation with CD40 L in vitro, the mRNA expression of AID in peripheral blood mononuclear cells (PBMCs) was decreased in patients with PNS compared with that in healthy controls. Our results indicate that the immunoglobulin CSR of B cells was partly dysfunctional and provide insights into the potential involvement of impaired TFH cell-dependent B cell responses in the pathogenesis of low IgG levels through downregulating CD40 L expression on TFH cells in PNS.
['Yang|Xia|X|', 'Tang|Xiaoxiao|X|', 'Li|Ting|T|', 'Man|Changming|C|', 'Yang|Xuejun|X|', 'Wang|Mo|M|', 'Zhang|Gaofu|G|', 'Chen|Yaxi|Y|', 'Yang|Haiping|H|', 'Li|Qiu|Q|']
D000293:Adolescent D001323:Autoantibodies D001402:B-Lymphocytes D023201:CD40 Ligand D002648:Child D002675:Child, Preschool D005260:Female D018858:Germinal Center D006801:Humans D007074:Immunoglobulin G D060889:Inducible T-Cell Co-Stimulator Protein D007223:Infant D007378:Interleukins D007963:Leukocytes, Mononuclear D008297:Male D009404:Nephrotic Syndrome D010950:Plasma Cells D006377:T-Lymphocytes, Helper-Inducer
Class-Switch recombination Primary nephrotic syndrome Low IgG CD40 ligand Follicular helper T cells