ANATOMY OF AUTOANTIBODY PRODUCTION - DOMINANT LOCALIZATION OF ANTIBODY-PRODUCING CELLS TO T-CELL ZONES IN FAS-DEFICIENT MICE

ANATOMY OF AUTOANTIBODY PRODUCTION - DOMINANT LOCALIZATION OF ANTIBODY-PRODUCING CELLS TO T-CELL ZONES IN FAS-DEFICIENT MICE
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DOI:
10.1016/1074-7613(95)90179-5
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发表时间:
1995-10-01
期刊:
影响因子:
32.4
通讯作者:
MARSHAKROTHSTEIN, A
MARSHAKROTHSTEIN, A
中科院分区:
医学1区
文献类型:
--
作者:
JACOBSON, BA;PANKA, DJ;MARSHAKROTHSTEIN, A

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本研究的目的是检查正常和自身免疫易感小鼠体内自身抗体产生的部位。用IgM和IgG 2a特异性核糖探针在组织切片中鉴定B细胞,所述核糖探针容易区分静息细胞与抗体形成细胞(AFC)。在正常小鼠中,在红髓中发现少数可识别的IgG 2a分泌细胞。相比之下,在lpr小鼠中,在富含T细胞的动脉周围淋巴鞘(帕尔斯)深处发现极高数量的IgG 2a和自身抗体产生细胞。分泌自身抗体的B细胞的这种不寻常的解剖学位置对于Fas失调的菌株是独特的,因为在MRL/+和(SWR x NZ B)F1小鼠中发现IgG 2a产生细胞主要在红髓或外部帕尔斯中,与正常小鼠相似。此外,对来自lpr和非lpr抗DNA免疫球蛋白转基因小鼠的脾脏的分析揭示了Tg(+)细胞仅在lpr小鼠的内部帕尔斯中的显著积累。这些数据表明,在Fas的情况下,自身反应性B细胞积累在T细胞丰富的区域,这种解剖特征可能有助于自身抗体的产生。
The goal of this study was to examine the in vivo site of autoantibody production in normal and autoimmune-prone mice. B cells were identified in tissue sections with IgM- and lgG2a-specific riboprobes that readily distinguished resting cells from antibody-forming cells (AFC). In normal mice, the few identifiable lgG2a-secreting cells were found in the red pulp. By contrast, in lpr mice exceedingly high numbers of IgG2a and autoantibody-producing cells were found deep within the T cell-rich periarteriolar lymphoid sheaths (PALS). This unusual anatomic location of autoantibody-secreting B cells is unique to Fas dysregulated strains, since IgG2a-producing cells in MRL/+ and (SWR x NZB)F1 mice were found predominantly in the red pulp or outer PALS, similar to normal mice, Furthermore, analysis of spleens from lpr and non-lpr anti-DNA immunoglobulin transgenic mice revealed dramatic accumulation of Tg(+) cells in the inner PALS only in lpr mice. These data suggest that in the absence of Fas, autoreactive B cells accumulate in T cell-rich zones, and this anatomic feature may contribute to autoantibody production.