Th2 cytokines increase and stimulate B cells to produce IgG4 in idiopathic membranous nephropathy

Abstract

These results indicate that the altered functions of T cells to produce Th2 cytokines and the increased production of IgG4 by B cells in response to these cytokines characterize the immune response in idiopathic membranous nephropathy.

Correlation between B Lymphocyte Abnormality and Disease Activity in Patients with Idiopathic Membranous Nephropathy

“…21 Studies have indicated that IgG4 occurs in the epithelium of the kidney of IMN patients. 22,23 Under the stimulation of interleukin-4 (IL-4) and IL-10 secreted by Th2 cells, IgG4 in B lymphocytes was up-regulated. 6 In addition, B lymphocytes are implicated in the development of renal injury as a result of their antigen-presenting role.…”

“…7 Antibodies are secreted by plasma cells that are derived from B lymphocytes, implying that B lymphocytes play an important role in the pathogenesis of IMN. Experiments showed the type 2 helper (Th2) T-cells were the dominant cell type in patients with IMN 8 and that the cytokines secreted by Th2 cells could promote the production of immunoglobulin (Ig) G4 type antibodies by B lymphocytes, 9 resulting in membranous nephropathy.…”

Rituximab Therapy in Idiopathic Membranous Nephropathy

“…In another study of MN patients, Kuroki et al demonstrated that T and B cell dysregulation results in Th2 predominance and appropriate cytokine secretion with a concomitant increase in production of IgG4 by B cells (12). Thus, because the mechanism of action of RTX in MN is unknown and response is incomplete (only two-thirds of patients respond), we conducted a systematic and serial evaluation of B and T cells before RTX and at defined intervals after treatment to determine whether baseline values or the kinetics of subpopulation recovery in B and/or T cells influenced clinical outcome.…”

Immunopathogenic Mechanism and Therapeutic Intervention in an Experimental Murine Model of Membranous Nephropathy

“…To our knowledge, the diversity of Th1/Th2 in MN is still controversial. Studies involving patients with idiopathic MN showed a consistently negative response for delay type hypersensitivity (DTH) effectors, an increase in IL-4 production by peripheral T helper cells; and a predominance of IgG4 (Th2-type subclass) as well as complement deposition in glomeruli; suggesting a Th2 response (Oliveira, 1998;Kuroki et al, 2005;Masutani et al, 2004;Hirayama et al, 2002;Doi et al, 1984;Doi et al, 1991;Haas, 1994;Imai et al, 1997;Iskandar et al, 1992;Roberts et al, 1983). The above findings favor Th2 response.…”