CD19+CD5+ B Cells in Primary IgA Nephropathy

• Published in: Journal of the American Society of Nephrology Vol. 19; no. 11; pp. 2130 - 2139
• Main Authors: HE YULING, XIAO RUIJING, BI YONGYI, XIA BING, WU XINXING, JIN YOUXIN, FOX, David A, LUNDY, Steven K, DING GUOHUA, TAN JINQUAN, JI XIANG, JIANG YANPING, CHEN LANG, LI LI, YANG DINGPING, TAN XINTI, LIU JINGYI, TANG ZHIQING
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01.11.2008; American Society of Nephrology
• Subjects: Adolescent; Adult; Antigens, CD19 - metabolism; Apoptosis; B-Lymphocyte Subsets - immunology; B-Lymphocyte Subsets - pathology; Base Sequence; Basic Research; Biological and medical sciences; Case-Control Studies; CD5 Antigens - metabolism; Cell Differentiation; DNA Primers - genetics; Female; Glomerulonephritis; Glomerulonephritis, IGA - etiology; Glomerulonephritis, IGA - immunology; Glomerulonephritis, IGA - pathology; Glomerulonephritis, IGA - therapy; Humans; Interferon-gamma - biosynthesis; Lupus Erythematosus, Systemic - immunology; Lupus Erythematosus, Systemic - pathology; Lymphocyte Activation; Male; Medical sciences; Middle Aged; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Kidney disease; Human; Immunopathology; Nephrology; Urinary system disease; Pathogenesis; Primary; IgA glomerular nephropathy; B-Lymphocyte; Urology
• ISSN: 1046-6673; 1533-3450
• DOI: 10.1681/ASN.2007121303

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-gamma, 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.