Functional implications of regulatory B cells in human IgA nephropathy.
IgA nephropathy (IgAN) diagnosis remains largely based upon immunohistologic detection of IgA- and IgG-containing glomerular deposits in renal mesangial cells, and little is known about the underlying pathogenic mechanisms. This study examines the putative contribution of B cell types, including the Breg type, to IgAN pathogenesis. Twenty-four patients with IgAN and proteinuria (Group A: <3.5 g/24 h, n = 13; Group B: >3.5 g/24 h, n = 11) and 10 healthy controls were enrolled. The frequencies of B cell subtypes in venous blood were measured by flow cytometry. Galactose-deficient IgA1 was measurement by ELISA. Needle biopsies were analysed by histology and immunofluorescence microscopy. Correlation between clinical features and B cell subtypes, including the regulatory B (Breg) cells, and Breg cell-derived immunomodulatory cytokine IL-10 was assessed by Spearman's rank correlation test. IgAN patients had significantly higher frequencies of CD27(+) CD19(+) , CD38(+) CD19(+) , CD86(+) CD19(+) and CD5(+) CD19(+) B cells than the healthy controls, but significantly lower levels of Breg cells and intracellular expression of IL-10 protein in the Breg subtype. Serum IgA concentration positively correlated with CD27(+) CD19(+) B cell frequency and negatively correlated with IL-10(+) Breg cell frequency in IgAN patients, and the percentage of CD19(+) CD5(+) CD1d(+) in CD19(+) cells was negatively correlated with the level of serum Gd-IgA1. Furthermore, the frequencies of CD19(+) CD38(+) and CD19(+) CD86(+) in the CD19(+) subpopulation negatively correlated with the estimated glomerular filtration rate of IgAN patients. Several of the CD19(+) B cell subtypes and the IL-10(+) Breg cells are differentially expressed in IgAN patients and may contribute to the disease pathogenesis.
Key Laboratory for Zoonosis Research, Department of Central Laboratory, Ministry of Education, The First Hospital of Jilin University, Changchun, China; Department of Nephropathy, Jining No. 1 People's Hospital, Shandong, China.
Y-Y
YY
Wang
L
L
Zhang
P-W
PW
Zhao
L
L
Ma
C
C
Li
H-B
HB
Zou
Y-F
YF
Jiang
D051997:ADP-ribosyl Cyclase 1 / Q000276:immunology / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D018941:Antigens, CD19 / Q000276:immunology / Q000378:metabolism; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D060151:B-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D051940:B7-2 Antigen / Q000276:immunology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D005690:Galactose / Q000172:deficiency; D005922:Glomerulonephritis, IGA / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000097:blood / Q000276:immunology / Q000378:metabolism; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
D018941:Antigens, CD19; D051940:B7-2 Antigen; D007070:Immunoglobulin A; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D016753:Interleukin-10; D051997:ADP-ribosyl Cyclase 1; D005690:Galactose