CD19+CD5+ B cells in primary IgA nephropathy.
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.
Yuling
He
H
Department of Immunology, Wuhan University School of Medicine, Wuhan University, Dong Hu Road 115, 430071 Wuchang, Wuhan, P.R. China.
Ruijing
Xiao
X
Xiang
Ji
J
Yanping
Jiang
J
Lang
Chen
C
Li
Li
L
Dingping
Yang
Y
Xinti
Tan
T
Jingyi
Liu
L
Zhiqing
Tang
T
Yongyi
Bi
B
Bing
Xia
X
Xinxing
Wu
W
Youxin
Jin
J
Fox
David A
DA
Lundy
Steven K
SK
Guohua
Ding
D
Jinquan
Tan
T
D000293:Adolescent; D000328:Adult; D018941:Antigens, CD19 / Q000378:metabolism; D017209:Apoptosis; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology; D001483:Base Sequence; D018956:CD5 Antigens / Q000378:metabolism; D016022:Case-Control Studies; D002454:Cell Differentiation; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005922:Glomerulonephritis, IGA / Q000209:etiology / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged
D018941:Antigens, CD19; D018956:CD5 Antigens; D017931:DNA Primers; D007371:Interferon-gamma