Anti-inflammatory curcumin inhibits AID expression within cycling human B cells

Abstract Curcumin is a natural phenolic compound extracted from the spice, Curcuma longa. It has noted anti-inflammatory effects, in part due to its suppression of NF-kB. Activation-induced cytosine deaminase (AID) is a NF-kB-regulated enzyme essential for Ig class switch recombination and somatic hyper-mutation with a demonstrated role in lymphomagenesis. This study has examined the effect of curcumin on the division-dependent upregulation of AID protein and mRNA within in vitro-activated normal human B lymphocytes and the AID-expressing B cell line, CL-01. CFSE-labeled, IgM+ human B2 cells isolated from spleen/tonsil were pre-activated for 4-5 days with stimuli likely encountered in sites of inflammation, i.e. limiting surrogate C3dg-coated antigen (anti-IgM: anti-CD21: dextran) + IL-4 + BAFF. Curcumin at doses from 6 to 50 µM, or parallel vehicle control, was pulsed into dividing B cell cultures and AID mRNA and protein were assessed after 1 or 2 d, respectively. Expression of mRNA was monitored by both quantitative and qualitative RT-PCR. AID protein was assessed, by two-color flow cytometry of CFSE-labeled cells and immunoblotting. Curcumin significantly down-regulated AID mRNA and protein, in dose dependent fashion. Accompanying this decline was a diminished recovery of IgG+ class-switched B cells within the divided population. This study suggests that curcumin could have a role in treating B cell autoimmune disease and reducing the risk of malignant transformation.