DNA SEQUENCES INVOLVED IN THE HEAVY CHAIN SWITCH

在免疫球蛋白产生细胞的抗原驱动分化期间， 可以发生从μ到γ、δ或重链合成转换。 这 蛋白质开关是DNA缺失的结果，该DNA缺失将V区从 C-γ、C-β或C-α基因的供体C-μ。 此删除开始于 并以开关片段结束，DNA区域由串联重复的 序列的我们的研究目的是详细研究小鼠 S-gamma片段 有兴趣在组织这一转变 片段，特别是在串联序列之间存在独特序列的情况下， 重复。 我们的计划包括：（1）仔细检查同源性 S-gamma-3、S-mu和S-gamma-1之间的关系，以便我们可以评估 S-gamma-3在mu到gamma转换中的作用;（2）建议克隆和 对五个表达的γ-3基因中的开关重组位点进行测序， 5个表达的γ-1基因（来自浆细胞瘤和杂交瘤）;（3） 询问在开关段（以唯一或重复的序列）中， 发生开关重组，且如果存在用于 不同于γ-1识别序列的γ-3转换位点 换个地方 如果重链转换是姐妹染色单体交换， 供体和受体转换区段之间的序列可以不 （4）试图识别、克隆和测序DNA片段， 来源于供体和受体转换片段之间， 保留在产生免疫球蛋白的杂交瘤的DNA中;（5） 了解开关重组酶的特异性和遗传学， 旨在选择组成型产生这些酶细胞系。 我们的研究表明开关重组酶催化c-myc-switch 部分重新安排。 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一过程中的作用， （6）筛选浆细胞瘤DNA中c-myc-kappa轻链 连锁重组，并确定此类重组的性质，如果 它们是存在的 （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)