Reap E A, Piecyk M L, Oliver A, Sobel E S, Waldschmidt T, Cohen P L, Eisenberg R A
Department of Medicine, University of North Carolina, Chapel Hill, 27599-7280, USA.
Clin Immunol Immunopathol. 1996 Jan;78(1):21-9. doi: 10.1006/clin.1996.0004.
Mice homozygous for the mutant Fas gene lpr develop generalized lymphoproliferation and produce autoantibodies resembling those found in human SLE. We have previously shown that these autoantibodies are produced by B2 cells rather than B1 cells and that the autoantibody- producing B cells are intrinsically abnormal. We investigated further the lpr B cell with a large panel of antibodies to B-cell surface markers to identify phenotypic abnormalities. B cells from spleen and bone marrow of age-matched congenic mice differing only at the lpr locus were examined by flow cytometry. Two consistent phenotypic differences were identified. First, spleen cells from older lpr mice had an increase in the number and percentage of IgM+ B cells expressing low levels of CD23. Second, lpr bone marrow had decreased numbers of B220hiIgM+-syndecan-1+CD23+ B cells. All other markers tested, except the previously identified modest increase of Ia on lpr spleen cells, showed no consistent differences. B cells from gld mice showed the same phenotypic abnormalities as those from lpr. Compared to T cells, the relative paucity of cell surface marker differences between lpr and +/+ B cells suggests that B cells may have fewer regulatory mechanisms to silence autoreactive specificities. The phenotypic differences identified may provide clues to the mechanism of autoantibody production in lpr mice, while the overwhelming phenotypic similarity between lpr and +/+ B cells suggests that the major abnormality of lpr B cells may lie in their specificity, that is, in their inability to delete autoreactive subsets.
纯合子突变型Fas基因lpr的小鼠会发生全身性淋巴细胞增殖，并产生类似于人类系统性红斑狼疮（SLE）中发现的自身抗体。我们之前已经表明，这些自身抗体是由B2细胞而非B1细胞产生的，并且产生自身抗体的B细胞本质上是异常的。我们使用大量针对B细胞表面标志物的抗体进一步研究lpr B细胞，以确定其表型异常。通过流式细胞术检测了仅在lpr位点存在差异的年龄匹配同基因小鼠脾脏和骨髓中的B细胞。确定了两个一致的表型差异。首先，老年lpr小鼠的脾脏细胞中，表达低水平CD23的IgM⁺ B细胞数量和百分比增加。其次，lpr骨髓中B220hiIgM⁺-syndecan-1⁺CD23⁺ B细胞数量减少。除了之前确定的lpr脾脏细胞上Ia适度增加外，所有其他测试的标志物均未显示出一致的差异。gld小鼠的B细胞表现出与lpr小鼠相同的表型异常。与T细胞相比，lpr和+/+ B细胞之间细胞表面标志物差异相对较少，这表明B细胞可能具有较少的调节机制来沉默自身反应性特异性。所确定的表型差异可能为lpr小鼠自身抗体产生的机制提供线索，而lpr和+/+ B细胞之间压倒性的表型相似性表明，lpr B细胞的主要异常可能在于其特异性，即在于它们无法清除自身反应性子集。
