STUDIES OF IMMUNOGLOBULIN GENE REARRANGEMENT

免疫球蛋白基因重排的研究

• 批准号: 3917766
• 负责人: M GELLERT
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3917766
• 关键词: B lymphocyte; antibody formation; bacterial DNA; bioassay; gene expression; gene rearrangement; genetic manipulation; immunoglobulins; laboratory mouse; molecular biology; nucleic acid sequence; plasmids; protein signal sequence; severe combined immunodeficiency; tissue /cell culture

Two new and unusual products of V(D)J recombination in lymphoid cells have been identified. Normal recombination joins the two signal sequences that identify the rearrangement site and, in the complementary reaction, joins the fragments of coding sequences that flank the signals. In extrachromosomal plasmid substrates, these products are found, but there is also a class of "hybrid joints" that link one signal to the coding flank of its partner signal. A second class of "open and shut" events rejoins each signal to its own flank, and is identifiable because of nucleotides lost and/or added at the joint. Both these products supply evidence that DNA strand alignment is not precisely specified in V(D)J recombination. A specific defect of V(D)J recombination has been identified in lymphoid cell lines derived from mice with the severe combined immune deficiency (scid) mutation. In extrachromosomal substrates, these cells make signal joints (though with greater imprecision than normal) but are unable to make coding joints. This failure appears sufficient to explain the absence of functional B and T cells in scid mice.

淋巴细胞中两种新的不寻常的V（D）J重组产物 细胞已被识别。 正常的重组将两者连接起来 识别重排位点的信号序列， 互补反应，连接编码序列的片段 信号的侧翼 在染色体外质粒底物中， 这些产品被发现，但也有一类“混合 将一个信号连接到另一个信号的编码侧翼的”接头 信号了 第二类“打开和关闭”事件重新连接每个 信号传递到它自己的侧翼，并且由于核苷酸 在连接处丢失和/或添加。 这两种产品供应 证据表明，DNA链排列并没有精确地指定在 V（D）J重组。 V（D）J重组的一个特殊缺陷已在 淋巴样细胞系来源于患有严重联合 免疫缺陷（SCID）突变。 在染色体外底物中， 这些细胞形成信号关节（尽管不精确 而不是正常的），但不能使编码关节。 该失效 似乎足以解释功能性B和T的缺失 scid小鼠中的细胞。