A REPERTOIRE OF MONOCLONAL-ANTIBODIES WITH HUMAN HEAVY-CHAINS FROM TRANSGENIC MICE
A REPERTOIRE OF MONOCLONAL-ANTIBODIES WITH HUMAN HEAVY-CHAINS FROM TRANSGENIC MICE
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DOI：
10.1073/pnas.86.17.6709
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发表时间：
1989-09-01
影响因子：
11.1
通讯作者：
NEUBERGER, MS
中科院分区：
文献类型：
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作者：
BRUGGEMANN, M;CASKEY, HM;NEUBERGER, MS
将人类免疫球蛋白基因片段以其未重排的构型引入小鼠的生殖系中可能允许产生人类抗体库。这种转基因小鼠可用于生产抗人抗原的人单克隆抗体。为了测试这种方法的可行性，创建了携带人重链微基因座的小鼠，该微基因座包含与人μ-连接的未重排的免疫球蛋白可变元件、多样性元件和连接元件链基因该微位点的基因片段在胸腺和脾脏的大部分细胞中重排，但在非淋巴组织中不重排。约4%的B淋巴细胞合成人μ产生约50 μ g转基因IgM抗体/ml的血清滴度。从稳定分泌几微克含有人μ l抗体的转基因小鼠建立杂交瘤。重链/毫升。
The introduction of human immunoglobulin gene segments in their unrearranged configuration into the germ line of mice might allow the production of a repertoire of human antibodies. Such transgenic mice could be used for the production of human monoclonal antibodies against human antigens. To test the feasibility of this approach, mice were created that carry a human heavy-chain minilocus comprising unrearranged immunoglobulin variable, diversity, and joining elements linked to a human .mu.-chain gene. The gene segments of this minilocus are rearranged in a large proportion of cells in thymus and spleen but not in nonlymphoid tissue. Some 4% of the B lymphocytes synthesize human .mu. chains resulting in a serum titer of about 50 .mu.g of transgenic IgM antibody per ml. Hybridomas were established from the transgenic mice that stably secreted several micrograms of antibodies containing human .mu. heavy chains per milliliter.