Ig heavy chain class switching in rag-deficient mice
Ig heavy chain class switching in rag-deficient mice
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DOI：
10.1093/intimm/10.3.325
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发表时间：
1998-03-01
影响因子：
4.4
通讯作者：
Alt, FW
中科院分区：
文献类型：
--
作者：
Lansford, R;Manis, JP;Alt, FW
为了研究RAG-1和RAG-2基因产物在IG重链类重组（CSR）中的潜在作用，我们已经产生了RAG-1（-/-）和RAG-2（-/-）小鼠，其含有重排的IG HC V（D）J基因（称为B1-8）插入内源性IG重链（HC）基因座中代替J（H）区段，和重排的λ 1轻链（LC）转基因（分别称为RAG-1（-/-）B1-8 λ和RAG-2（-/-）B1-8 λ小鼠），B1-8 HC基因和λ LC基因编码结合形成完整IG分子的蛋白质，其表达导致RAG-1（-/-）B1-8 λ和RAG-2（-/-）B1-8 λ小鼠的外周B细胞区室的基本重建，RAG-1（-/-）B1-8 λ和RAG-2（-/-）B1-8 λ小鼠都具有相对正常水平的各种IgG同种型，但与正常同窝出生的小鼠相比，血清IgM和伊加水平大大降低。用脂多糖（LPS）或LPS加IL-4体外活化的RAG-1（-/-）B1-8 λ和RAG-2（-/-）B1-8 λ B细胞在IgG 3、IgG 1、IgG 2 B b、IgG 2 a和IgE的表面表达和分泌方面与对照B细胞的反应相似，但IgM的分泌也有缺陷。这些发现表明，在B细胞中，RAG-1和RAG-2的表达对于向大多数HC同种型的有效类别转换都不是必需的。
To investigate potential roles of the RAG-1 and RAG-2 gene products in Ig heavy chain class recombination (CSR), we have generated RAG-1(-/-) and RAG-2(-/-) mice which contain both a rearranged Ig HC V(D)J gene (referred to as B1-8) inserted into the endogenous Ig heavy chain (HC) locus in place of the J(H) segments, and a rearranged lambda 1 light chain (LC) transgene (which are referred to as RAG-1(-/-)B1-8 lambda and RAG-2(-/-)B1-8 lambda mice respectively), The B1-8 HC gene and lambda LC genes encode proteins that associate to form a complete Ig molecule, the expression of which leads to substantial reconstitution of the peripheral B cell compartments of RAG-1(-/-)B1-8 lambda and RAG-2(-/-)B1-8 lambda mice, Both RAG-1(-/-)B1-8 lambda and RAG-2(-/-)B1-8 lambda mice have relatively normal levels of the various IgG isotypes, but greatly reduced levels of serum IgM and IgA compared to normal littermates, Furthermore, RAG-1(-/-)B1-8 lambda and RAG-2(-/-)B1-8 lambda B cells activated in vitro with lipopolysaccharide (LPS) or LPS plus IL-4 responded similarly to control B cells with respect to surface expression and secretion of lgG3, IgG1, IgG2b, IgG2a and IgE, but again were deficient in the secretion of IgM, Together, these findings indicate that neither RAG-1 nor RAG-2 expression is required for efficient class switching to most HC isotypes in B cells.