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AB0207 Impaired inhibition on B cell activation by bone marrow-derived mesenchymal stem cells with decreased CCL2 expression in MRL/LPR mice
  1. N. Che,
  2. X. Li,
  3. L. Sun
  1. The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China

Abstract

Background Bone marrow–derived mesenchymal stem cells (BM-MSCs) are multipotent cells characterized by immunomodulatory properties and are therefore considered as a promising cell therapy for autoimmune diseases. It has been shown that BM-MSCs from healthy donors were able to inhibit the activation of B cells in vitro and in vivo. Our previous study revealed that BM-MSCs from patients with systemic lupus erythematosus (SLE) possessed some dysfunctions.

Objectives This study aimed to assess whether inhibition on B cell activation by BM-MSCs in MRL/lpr mice, an animal model of SLE, was impaired and the possible mechanisms involved in this process.

Methods BM-MSCs were isolated and expanded from either C57BL/6J or MRL/lpr mice. The effects of BM-MSCs on the proliferation and differentiation to plasma cells of normal splenic B cell isolated from C57BL/6J mice were evaluated in vitro. And the differential expression of CCL2 on BM-MSCs from C57BL/6J or MRL/lpr mice was detected. Lupus mice were treated with these two different BM-MSCs respectively, and the levels of serum auto-antibodies and immunoglobulin deposition in the kidney were monitored.

Results BM-MSCs from C57BL/6J mice inhibited the proliferation and differentiation to plasma cells of B cells in vitro. This inhibitory effect was mediated by soluble factors, including CCL2, as neutralizing CCL2 could abolish the suppressive effect on B cells mediated by normal BM-MSCs. Inhibition on B-cell proliferation and differentiation by BM-MSCs from MRL/lpr mice was impaired, partially resulted from down-regulated expression of CCL2. The addition of processed CCL2 restored inhibitory effects of BM-MSCs from MRL/lpr mice on B-cells. In vivo treatment with BM-MSCs from MRL/lpr mice did not reduce the levels of serum pathological antibody production and immunoglobulin deposition in the kidney compared with treatment with BM-MSCs from C57BL/6J mice.

Conclusions Our findings suggest that inhibitory effects of BM-MSCs on B-cell are mediated by soluble factors including CCL2. Impaired inhibition of BM-MSCs from MRL/lpr mice on B-cell maybe attributes to the down-regulation of CCL2 expression, which may play an important role in the pathogenesis of SLE.

Disclosure of Interest None Declared

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