DNA SEQUENCES INVOLVED IN THE HEAVY CHAIN SWITCH

在抗原驱动的免疫球蛋白产生细胞分化过程中， 可以发生从µ到伽马、增量或重链合成的切换。这 蛋白质开关是DNA缺失的结果，它将V区从 C-Gamma、C-epsilon或C-α基因的供体C-Mu。此删除操作开始 末端在开关片段中，DNA区域由重复的DNA组成 序列。我们的调查旨在详细研究小鼠的序列 S-伽马段。人们对此交换机的组织很感兴趣 片段，特别是在串联序列中存在唯一序列的情况下 重复着。我们的计划包括：(1)仔细检查同源性 S-伽马-3，S-木，S-伽马-1之间的关系，以便我们可以评估 S-伽马-3在Mu到Gamma开关中的作用；(2)提出克隆和 对5个表达的Gamma-3基因中的开关重组位点进行测序 5个表达伽马-1基因(来自浆细胞瘤和杂交瘤)； 询问交换数据段中的位置(在唯一或重复的序列中) 切换重组发生，如果存在识别序列 不同于伽马-1识别序列的伽马-3开关位点 换个位置。如果重链开关是S姐妹染色单体交换， 供体和受体开关片段之间的序列可能不是 删除；(4)试图识别、克隆和测序下列DNA片段 派生自供体和受体交换数据段之间，但 保留在产生免疫球蛋白的杂交瘤DNA中；(5) 为了了解开关重组酶的特异性和遗传学，我们 意欲选择一种构成产生这些酶的细胞系。 我们的研究表明Switch重组酶催化c-myc-Switch 分段重排。如果易位到轻链基因座 浆细胞瘤反映c-myc-轻链重排， 很难理解开关重组酶在这方面的作用 重排；以及(6)为c-myc-kappa光筛选浆细胞瘤DNA 链重组并确定这种重组的性质，如果 他们是存在的。(IS)

During antigen-driven differentiation of immunoglobulin-producing cells, a switch from mu to gamma, delta, or a heavy chain synthesis can occur. This protein switch is the result of a DNA deletion that moves a V region from a donor C-mu to a C-gamma, C-epsilon, or C-alpha gene. This deletion begins and ends in switch segments, DNA regions composed of tandemly repeated sequences. Our investigation aims to study in detail the sequence of murine S-gamma segments. There is interest in the organization of this switch segment, particularly in the presence of unique sequences among the tandem repeats. Our plans include: (1) examining carefully the homology relationships among S-gamma-3, S-mu, and S-gamma-1 so that we can evaluate the role of S-gamma-3 in mu to gamma switches; (2) proposing to clone and sequence the switch recombination sites in five expressed gamma-3 genes and five expressed gamma-1 genes (from both plasmacytomas and hybridomas); (3) asking where in the switch segments (in unique or repeated sequences) the switch recombinations take place and if there is a recognition sequence for gamma-3 switch sites different from a recognition sequence for gamma-1 switch sites. If the heavy chain switch is s sister chromatid exchange, sequences between the donor and recipient switch segments may not be deleted; (4) attempting to identify, clone, and sequence DNA fragments that are derived from between donor and recipient switch segments but are retained in the DNA of immunoglobulin-producing hybridomas; (5) understsnding the specificity and genetics of switch recombinases, we intend to select a cell line that constitutively produces these enzymes. Our research suggests that switch recombinases catalyze c-myc-switch segment rearrangements. If translocations to the light chain locus in plasmacytomas reflect c-myc-light chain rearrangements, it would be difficult to understand the role of switch recombinases in this rearrangement; and (6) screening plasmacytoma DNAs for c-myc-kappa light chain recombinations and determining the nature of such recombinations if they exist. (IS)