ENFORCED BCL2 EXPRESSION IN B-LYMPHOID CELLS PROLONGS ANTIBODY-RESPONSES AND ELICITS AUTOIMMUNE-DISEASE
ENFORCED BCL2 EXPRESSION IN B-LYMPHOID CELLS PROLONGS ANTIBODY-RESPONSES AND ELICITS AUTOIMMUNE-DISEASE
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DOI：
10.1073/pnas.88.19.8661
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发表时间：
1991-10-01
影响因子：
11.1
通讯作者：
HARRIS, AW
中科院分区：
文献类型：
--
作者：
STRASSER, A;WHITTINGHAM, S;HARRIS, AW
BCL 2基因的生物学功能进行了研究，在转基因小鼠携带人BCL 2 cDNA的免疫球蛋白重链增强子（E-mu）的控制下。代表性转基因品系E-mu-bcl-2-22的小鼠具有大量过量的B淋巴细胞、免疫球蛋白分泌细胞和血清免疫球蛋白，这归因于B系细胞寿命的延长。前B细胞和浆细胞以及B细胞在培养物中表现出延长的存活。免疫动物产生了放大和延长的抗体反应。在生命的第一年内，大多数小鼠自发地产生针对核抗原的抗体，60%的小鼠发展为肾脏疾病，诊断为免疫复合物肾小球肾炎。因此，E-mu-bcl-2-22小鼠构成了类似于人类疾病系统性红斑狼疮的系统性自身免疫疾病的转基因模型。
The biological functions of the BCL2 gene were investigated in transgenic mice harboring human BCL2 cDNA under the control of an immunoglobulin heavy chain enhancer (E-mu). Mice of a representative transgenic strain, E-mu-bcl-2-22, had a great excess of B lymphocytes, immunoglobulin-secreting cells, and serum immunoglobulins, attributable to increased longevity of B-lineage cells. Pre-B and plasma cells as well as B cells exhibited prolonged survival in culture. Immunized animals produced an amplified and protracted antibody response. Within the first year of life, most mice spontaneously produced antibodies to nuclear antigens, and 60% developed kidney disease, diagnosed as immune complex glomerulonephritis. Thus E-mu-bcl-2-22 mice constitute a transgenic model for a systemic autoimmune disease resembling the human disorder systemic lupus erythematosus.