Increased frequency of surface IgA-positive plasma cells in the intestinal lamina 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 deposition to the kidney in hyper IgA (HIGA) mice, which was established as a mouse model for human IgA nephropathy with hyperserum IgA. The number of surface IgA+B220- lymphocytes in the intestinal lamina propria (LP) of HIGA mice increased 2.7-fold at 30 wk of age as compared with those at 10 wk of age, whereas normal mice did not show such increase. The surface IgA+B220- LP lymphocytes spontaneously secreted IgA in culture. Morphological studies 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 peritoneal B-1 cells. Cell cycle study on intestinal IgA-PCs using bromodeoxyuridine 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 enhanced proliferation or prolonged survival of IgA-producing PCs in LP. In addition, 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 IgA in HIGA mice and resultant IgA deposition to the kidney.
Kamata
T
T
Department of Medical Chemistry, Kyoto University Faculty of Medicine, Kyoto, Japan.
Nogaki
F
F
Fagarasan
S
S
Sakiyama
T
T
Kobayashi
I
I
Miyawaki
S
S
Ikuta
K
K
Muso
E
E
Yoshida
H
H
Sasayama
S
S
Honjo
T
T
D000818:Animals; D002453:Cell Cycle / Q000276:immunology; D005243:Feces / Q000737:chemistry; D005260:Female; D005922:Glomerulonephritis, IGA / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D007070:Immunoglobulin A / Q000096:biosynthesis* / Q000097:blood / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010950:Plasma Cells / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D011947:Receptors, Antigen, B-Cell / Q000096:biosynthesis* / Q000097:blood; D019056:Receptors, Polymeric Immunoglobulin / Q000096:biosynthesis / Q000235:genetics; D013045:Species Specificity
D007070:Immunoglobulin A; D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell; D019056:Receptors, Polymeric Immunoglobulin; C034639:polymeric IgA; D017493:Leukocyte Common Antigens