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 t onsillar focal infection. The comprehensive mechanism underlying this disea se remains to be defined. To better understand its pathogenesis, we investi gated tonsillar CD5(+) B cells (B-1 cells) with respect to IgA synthesis. G erminal 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 incu bated with agonist anti-CD40 MoAb and the ability for antibody production b y 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 a nd B-2 cells was analysed by flow cytometry. Although B-1 cells do not usua lly take part in the GC reaction, an increase in B-1 cell numbers was obser ved in the GC of tonsils from IgAN patients. These B-1 cells were likely Ig A1 antibody-producing cells, since the prominent IgA subclass in IgAN is ge nerally considered to be IgA1. Although Fas-dependent apoptosis is essentia l for the elimination of activated B cells, these B-1 cells showed a reduce d susceptibility to Fas-mediated apoptosis. It is conceivable that activate d B-1 cells may survive in the GC due to impaired apoptosis and thus produc e 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.