Kakkanaiah V N, Sobel E S, MacDonald G C, Cheek R L, Cohen P L, Eisenberg R A
Department of Medicine, University of North Carolina at Chapel Hill, 27599, USA.
J Immunol. 1997 Jul 15;159(2):1027-35.
Anti-Sm Abs are specific markers of human systemic lupus erythematosus (SLE) and of murine models of this disease. In humans, anti-Sm Abs are mostly IgG1, and in MRL/lpr mice, IgG2a; both are T-dependent isotypes. Other lpr strains, such as B6/lpr, do not produce anti-Sm Ab spontaneously. The present study was aimed at identifying the cellular expression of background genes responsible for generation of the anti-Sm Ab response in MRL/lpr mice. We used double chimeric mice made by transferring MRL/lpr and B6/lpr bone marrows into irradiated allotype heterozygous F1 mice. Five mo after reconstitution, FACS analysis of lymph node (LN) and spleen cells revealed that both MRL/lpr and B6/lpr cells coexisted in roughly equal numbers. Ab produced by each donor could be distinguished by allotype-specific assays. IgG2a anti-Sm was made only by MRL-derived B cells despite the presence of T cells that might potentially provide help to the B6/lpr B cells. The frequency of anti-Sm Ab-producing individuals was similar to that of unmanipulated MRL/lpr mice (about 25%). IgG2a anti-chromatin and total IgG2a was mostly dominated by the MRL-derived B cells. B6-derived B cells produced more rheumatoid factor (RF) against their own IgG2b(b), while RF against IgG2a was dominated by MRL-derived B cells. This suggests that the control of the production of particular autoantibody specificities, such as anti-Sm, is determined by the expression of MRL or B6 background genes in B cells.
抗Sm抗体是人类系统性红斑狼疮（SLE）及其小鼠模型的特异性标志物。在人类中，抗Sm抗体主要为IgG1，在MRL/lpr小鼠中则为IgG2a；二者均为T细胞依赖型同种型。其他lpr品系，如B6/lpr，不会自发产生抗Sm抗体。本研究旨在确定负责MRL/lpr小鼠抗Sm抗体应答产生的背景基因的细胞表达情况。我们使用了将MRL/lpr和B6/lpr骨髓移植到经辐照的异型杂合F1小鼠体内制成的双嵌合小鼠。重建后5个月，对淋巴结（LN）和脾细胞进行的流式细胞术分析显示，MRL/lpr和B6/lpr细胞以大致相等的数量共存。每种供体产生的抗体可通过同种型特异性检测加以区分。尽管存在可能为B6/lpr B细胞提供帮助的T细胞，但仅MRL来源的B细胞产生IgG2a抗Sm抗体。产生抗Sm抗体的个体频率与未处理的MRL/lpr小鼠相似（约25%）。IgG2a抗染色质和总IgG2a大多由MRL来源的B细胞主导。B6来源的B细胞产生更多针对自身IgG2b(b)的类风湿因子（RF），而针对IgG2a的RF则由MRL来源的B细胞主导。这表明特定自身抗体特异性（如抗Sm抗体）产生的控制是由B细胞中MRL或B6背景基因的表达所决定的。
