SEVERE COMBINED IMMUNODEFICIENCY IN THE MOUSE

我们最近报道了一种常染色体隐性突变， 联合免疫缺陷病（SCID）。 受影响的小鼠是 严重缺乏T和B淋巴细胞， 免疫力，易受致病病毒感染，或 细菌 为了确保它们的存活，SCID小鼠被保存在一个“干净”的环境中。 环境中没有病原微生物。 SCID小鼠是 重要的是，它使我们能够研究一个基因位点， 淋巴样分化，并作为类似疾病的模型 人类的综合症 我们已经证明，SCID突变阻断淋巴分化， 成熟 理解这种缺陷的本质的一个策略是 表征代表在SCID小鼠中停滞的那些淋巴样细胞。 因此，我们正在分析通过以下方法获得的早期前B细胞系： 用Abelson鼠白血病病毒转化SCID骨髓细胞。 已经用对Cmu特异的探针分析了五个Abelson系， IgH基因座的JH区域。 所有五个显示IgH重排，但在 所有至少一个IgH等位基因似乎缺失了其Jh区。 等 在来自正常小鼠骨的Abelson系中未观察到缺失 骨髓 这些数据表明在SCID小鼠早期B细胞中IgH重排 可能比正常小鼠更容易出错。 类似的分析在 使用对SCID T细胞淋巴瘤具有特异性的类似探针的研究进展 不beta 编码T细胞上抗原受体β链的基因座 这些淋巴瘤在SCID小鼠中自发产生，似乎来源于 胸腺中常见的未成熟T细胞。 理解SCID病变效应的第二个策略是表征 逃避或绕过成熟阻滞的淋巴样细胞。 存在 因为血清免疫球蛋白可以在这些细胞中检测到， 10 - 15%的SCID小鼠。 其中一些老鼠产生的能量是 正常小鼠中发现的IG量。 负责的细胞是否 正常与否尚不清楚，我们将继续调查病因， 这类Ig产生细胞的性质。

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.