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CD19⁺CD5⁺ B Cells in Primary IgA Nephropathy

He Yuling^*,, Xiao Ruijing^*,, Ji Xiang^*,, Jiang Yanping^*, Chen Lang^*,, Li Li^*,, Yang Dingping, Tan Xinti^*, Liu Jingyi^*, Tang Zhiqing^*,, Bi Yongyi^*, Xia Bing, Wu Xinxing^*, Jin Youxin, David A. Fox^*, Steven K. Lundy^*, Ding Guohua and Tan Jinquan^*,

^* Department of Immunology and Laboratory of Allergy and Clinical Immunology, Institute of Allergy and Immune-Related Diseases and Center for Medical Research, Wuhan University School of Medicine, and Section of Nephrology, Department of Internal Medicine, Renmin Hospital, and Departments of Internal Medicine and Geriatrics, Zhongnan University Hospital, Wuhan University, Wuhan, and State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Science, Shanghai, China

Correspondence to: Dr. Tan Jinquan, Department of Immunology, Wuhan University School of Medicine, Wuhan University, Dong Hu Road 115, 430071 Wuchang, Wuhan, P.R. China. Phone: +86-27-68758600; Fax: +86-27-68759222; E-mail: jinquan_tan{at}whu.edu.cn; or Dr. Ding Guohua, Section of Nephrology, Department of Internal Medicine, Renmin Hospital, Wuhan University 430071 Wuhan, P.R. China. Phone: +86-27-88041191-2415; Fax: +86-27-68759039; E-mail: DGX1010{at}yahoo.com

Received for publication December 10, 2007. Accepted for publication May 21, 2008.

The source of IgA and the mechanism for deposition of IgA in the mesangium remain unknown for primary IgA nephropathy. Because CD19⁺CD5⁺ B cells are important producers of IgA and contribute to several autoimmune diseases, they may play an important role in IgA nephropathy. In this study, flow cytometry, quantitative PCR, and confocal microscopy were used to assess the frequency, distribution, Ig production, CD phenotypes, cytokine production, and sensitivity to apoptosis of CD19⁺CD5⁺ B cells in the peripheral blood, peritoneal fluid, and kidney biopsies of 36 patients with primary IgA nephropathy. All patients with IgA nephropathy were significantly more likely to have CD19⁺CD5⁺ B cells in the peripheral blood, peritoneal fluid, and kidney biopsies than were five control subjects and 10 patients with active systemic lupus erythematosus. The 33 patients who had IgA nephropathy and responded to treatment demonstrated a significant decrease in CD19⁺CD5⁺ B cells in the peripheral blood, peritoneal fluid, and kidney (all P < 0.01). In the three patients who had IgA nephropathy and did not respond to treatment, the frequency of CD19⁺CD5⁺ B cells did not change. CD19⁺CD5⁺ B cells isolated from patients with untreated IgA nephropathy expressed higher levels of IgA, produced more IFN-, and were more resistant to CD95L-induced apoptosis than cells isolated from control subjects and patients with lupus; these properties reversed with effective treatment of IgA nephropathy. In conclusion, these results strongly suggest that CD19⁺CD5⁺ B cells play a prominent role in the pathogenesis of primary IgA nephropathy.

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673