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
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
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DOI：
10.4049/jimmunol.165.3.1387
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发表时间：
2000-08-01
影响因子：
4.4
通讯作者：
Honjo, T
中科院分区：
文献类型：
--
作者：
Kamata, T;Nogaki, F;Honjo, T
由于在人IgA肾病中已提示粘膜免疫异常，因此我们在高IgA（HIGA）小鼠中检查了粘膜免疫在IgA沉积到肾脏中的参与情况，该小鼠被建立为高血清IgA的人IgA肾病小鼠模型，表面IgA（+）B220（-）淋巴细胞的数量 HIGA小鼠的肠固有层（LP）在30周龄时比10周龄时增加了2.7倍，而正常小鼠则没有表现出这种增加。培养物中表面IgA(+)B220(-) LP淋巴细胞自发分泌IgA，形态学研究表明小鼠肠道LP的表面IgA(+)B220(-)淋巴细胞与浆细胞(PC)相同，LP中约20%的IgA(+)B220(-) PC同时表达Mac-1和CD19，提示它们可能 来源于腹膜 B-l 细胞，使用溴脱氧尿苷对肠道 IgA-PC 进行细胞周期研究，结果显示 HIGA 小鼠和正常小鼠之间没有差异，这表明 HIGA 小鼠中产生 IgA 的 PC 的高频率并不是由于 LP 中产生 IgA 的 PC 增殖增强或存活时间延长，此外，IgA 分泌到 HIGA 的肠腔中 随着年龄的增长，小鼠的数量急剧减少（降至四分之一）。这些数据表明，肠道产生 IgA 的 PC 数量增加和 IgA 排泄到肠腔的下调可能协同促进 HIGA 小鼠中血清 IgA 过多以及由此导致的 IgA 沉积到肾脏。
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-l 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.