Increase in tonsillar germinal centre B-1 cell numbers in IgA nephropathy (IgAN) patients and reduced susceptibility to Fas-mediated apoptosis.
IgAN is a common form of primary glomerulonephritis and also a disease of tonsillar focal infection. The comprehensive mechanism underlying this disease remains to be defined. To better understand its pathogenesis, we investigated tonsillar CD5+ B cells (B-1 cells) with respect to IgA synthesis. Germinal centre (GC) B cells were isolated from the tonsils of IgAN patients and the number of B-1 cells in the GC determined by flow cytometry. GC B-1 and B-2 (CD5- B) cells were purified by cell sorter, the cells were incubated with agonist anti-CD40 MoAb and the ability for antibody production by B-1 and B-2 cells determined by ELISPOT assay. GC B-1 cells and B-2 cells were incubated with agonist anti-Fas MoAb, and apoptosis in GC B-1 cells and B-2 cells was analysed by flow cytometry. Although B-1 cells do not usually take part in the GC reaction, an increase in B-1 cell numbers was observed in the GC of tonsils from IgAN patients. These B-1 cells were likely IgA1 antibody-producing cells, since the prominent IgA subclass in IgAN is generally considered to be IgA1. Although Fas-dependent apoptosis is essential for the elimination of activated B cells, these B-1 cells showed a reduced susceptibility to Fas-mediated apoptosis. It is conceivable that activated B-1 cells may survive in the GC due to impaired apoptosis and thus produce abnormal antibodies. These findings suggest that the immune responses of B-1 cells in the tonsillar GC could thus have an impact on the pathogenesis of IgAN.
Kodama
S
S
Department of Otolaryngology, Oita Medical University, Hazama-machi, Oita, Japan.
Suzuki
M
M
Arita
M
M
Mogi
G
G
D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000276:immunology*; D002452:Cell Count; D005260:Female; D018858:Germinal Center / Q000276:immunology / Q000473:pathology*; D005922:Glomerulonephritis, IGA / Q000276:immunology / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D014066:Palatine Tonsil / Q000276:immunology / Q000473:pathology; D019014:fas Receptor / Q000276:immunology
D019014:fas Receptor