Increased frequency of surface IgA-positive plasma cells in the intestinallamina propria and decreased IgA excretion in hyper IgA, (HIGA) mice, a murine model of IgA nephropathy with hyperserum IgA

Because abnormalities of mucosal immunity have been suggested in human IgA nephropathy, we examined the involvement of mucosal immunity in IgA deposit ion to the kidney in hyper IgA (HIGA) mice, which was established as a mous e model for human IgA nephropathy with hyperserum IgA, The number of surfac e IgA(+)B220(-) lymphocytes in the intestinal lamina propria (LP) of HIGA m ice increased 2.7-fold at 30 wk of age as compared with those at 10 wk of a ge, whereas normal mice did not show such increase. The surface IgA(+)B220( -) LP lymphocytes spontaneously secreted IgA in culture, Morphological stud ies showed that the surface IgA(+)B220(-) lymphocytes of murine intestinal LP are identical with plasma cells (PCs), About 20% of IgA(+)B220(-) PC in LP expressed both Mac-1 and CD19, suggesting that they may derive from peri toneal B-l cells, Cell cycle study on intestinal IgA-PCs using bromodeoxyur idine revealed no difference between HIGA mice and normal mice, suggesting that the high frequency of IgA-producing PCs in HIGA mice is not due to enh anced proliferation or prolonged survival of IgA-producing PCs in LP, In ad dition, IgA secretion into the gut lumen of HIGA mice decreased drastically (to one forth) with aging. These data suggest that the increased number of intestinal IgA-producing PCs and the down-regulation of IgA excretion into the intestinal lumen might synergistically contribute to the hyperserum Ig A in HIGA mice and resultant IgA deposition to the kidney.