SEVERE COMBINED IMMUNODEFICIENCY

我们最近报道了一种常染色体隐性遗传突变，导致严重的 小鼠的联合免疫缺陷病(SCID)。受影响的小鼠有 T和B淋巴细胞严重缺乏，几乎没有或没有 免疫力，很容易被致病病毒或 细菌。为了确保它们的生存，SCID小鼠被保持在一个干净的环境中 环境，没有致病微生物。SCID鼠标是 重要的是，它使我们能够研究控制早期 淋巴分化，并作为类似疾病的模型 人类的综合症。 我们已经证明，SCID突变阻止了淋巴分化和 成熟。要理解这种缺陷的本质，一种策略是 描述在SCID小鼠中滞留的代表淋巴样细胞的特征。 因此，我们正在分析通过以下方法获得的早期前B细胞株 用Abelson小鼠白血病病毒转化SCID骨髓细胞。 五条Abelson线已经用CMU和 IgH基因座的JH区。所有五个都显示了IGH的重新安排，但在 所有至少一个IGH等位基因似乎都删除了它的JH区域。是这样的 在来自正常小鼠骨骼的Abelson系中未发现缺失 骨髓。这些数据提示SCID小鼠早期B细胞中的IgH重排 可能比正常小鼠更容易出错。类似的分析也在 使用针对SCID T细胞淋巴瘤的类似探针的研究进展 编码T细胞表面抗原受体β链的Tβ基因座 细胞。这些淋巴瘤自发发生在SCID小鼠身上，似乎 来源于胸腺中常见的未成熟T细胞。 理解SCID损伤效应的第二个策略是 逃逸或绕过成熟块的淋巴样细胞。他的存在 是因为血清免疫球蛋白可以在 10%至15%的SCID小鼠。其中一些小鼠的产量是 在正常小鼠体内发现的Ig的数量。无论负责的细胞是 正常与否尚不清楚，我们正在继续调查病因和 这种产生免疫球蛋白的细胞的性质。(磅)

We recently reported an autosomal-recessive mutation causing severe combined immunodeficiency disease (SCID) in mice. Affected mice are severely deficient in T and B lymphocytes and they have little or no immunity, readily succumbing to infections by pathogenic viruses or bacteria. To ensure their survival, SCID mice are kept in a "clean" environment, free of pathogenic microorganisms. The SCID mouse is important for it enables us to study a genetic locus that controls early lymphoid differentiation and serves as a model for a similar disease syndrome in humans. We have shown that the scid mutation blocks lymphoid differentiation and maturation. One strategy for understanding this defect's nature is to characterize lymphoid cells representative of those arrested in SCID mice. Accordingly, we are analyzing early pre-B cell lines obtained by transforming SCID bone marrow cells with Abelson murine leukemia virus. Five Abelson lines have been analyzed with probes specific for the Cmu and the JH regions of the IgH locus. All five show IgH rearrangements, but in all at least one IgH allele appears to have deleted its Jh region. Such deletions are not seen in Abelson lines derived from normal mice bone marrow. These data suggest IgH rearrangements in SCID mouse early B cells may be more error-prone than in normal mice. Similar analyses are in progress with SCID T-cell lymphomas using analogous probes specific for the Tbeta locus which codes for the beta chain of antigen receptors on T cells. These lymphomas arise spontaneously in SCID mice and appear to derive from immature T cells routinely found in the thymus. A second strategy for understanding scid lesion effects is to characterize lymphoid cells that escape or bypass the maturation block. The existence of such cells is inferred because serum immunoglobulin can be detected in 10 to 15% of SCID mice. Some of these mice produce 3 to 4 times the quantity of Ig found in normal mice. Whether the cells responsible are normal or not is not clear, and we continue to investigate the etiology and nature of such Ig-producing cells. (LB)