A new murine model of humoral immuno-deficiency specifically affects class switching to T-independent antigens.
A new murine model of humoral immuno-deficiency specifically affects class switching to T-independent antigens.
复制标题
一种新的体液免疫缺陷小鼠模型特别影响向 T 独立抗原的类别转换。
DOI：
10.1002/eji.200425060
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Bottaro,Andrea
中科院分区：
文献类型：
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作者：
Kuzin,IgorI;Ugine,GregoryD;Barth,RichardK;Shultz,LeonardD;Nahm,MoonH;Young,FaithM;Bottaro,Andrea
免疫球蛋白（IG）同种型缺陷是最常见和最不典型的体液免疫缺陷之一。由于其极端的异质性和缺乏合适的动物模型，对其免疫学和遗传学特征的深入了解受到阻碍。在这里，我们报告了一个新的小鼠模型与选择性IG缺陷的初步表征。SENCARA小鼠显示出低血清IgG 3水平以及对T细胞非依赖性（TI）1型和2型抗原的IgG 3应答严重缺陷。 然而，尽管类别转换显著阻断，但TI抗原免疫后活化诱导的脱氨酶表达和γ3生殖系转录正常。对体外LPS刺激的IgG 3产生也是正常的，排除了Cγ3开关机制的特定缺陷。观察到腹膜B1 a细胞数量减少和脾边缘区扩大。免疫缺陷在SENCARA × C57 BL/6杂交中作为常染色体、半显性、基本上单基因性状遗传。 SENCARA体液免疫缺陷构成了一种新的免疫表型，类似于人类疾病，如IgG 2缺乏症。这种新的小鼠模型将感兴趣的TI免疫反应参与的机制的理解，并可能提供新的见解人类IG缺陷的分子基础。
Immunoglobulin (Ig) isotype deficiencies are among the most common and least characterized humoral immunodeficiencies. A thorough understanding of their immunological and genetic features has been hampered by their extreme heterogeneity and the paucity of suitable animal models. Here, we report the initial characterization of a new mouse model with selective Ig deficiency. SENCARA mice display low serum IgG3 levels as well as severely deficient IgG3 responses to T cell‐independent (TI) type 1 and 2 antigens. However, despite the significant block in class switching, expression of activation‐induced deaminase and γ3 germ‐line transcription after TI antigen immunization are normal. IgG3 production in response toin vitroLPS stimulation was also normal, ruling out a specific defect in the Cγ3 switch machinery. A decrease in the number of peritoneal B1a cells and enlarged splenic marginal zones were observed. The immunodeficiency is inherited as an autosomal, semi‐dominant, essentially monogenic trait in SENCARA × C57BL/6 crosses. The SENCARA humoral immunodeficiency constitutes a novel immune phenotype, resembling human conditions such as IgG2 deficiency. This new mouse model will be of interest for the understanding of mechanisms involved in TI immune responses and may provide new insights into the molecular basis of human Ig deficiencies.