ELIMINATION OF SELF-REACTIVE LYMPHOCYTES-B PROCEEDS IN 2 STAGES - ARRESTED DEVELOPMENT AND CELL-DEATH
ELIMINATION OF SELF-REACTIVE LYMPHOCYTES-B PROCEEDS IN 2 STAGES - ARRESTED DEVELOPMENT AND CELL-DEATH
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DOI：
10.1016/0092-8674(93)90111-3
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发表时间：
1993-02-12
期刊：
影响因子：
64.5
通讯作者：
GOODNOW, CC
中科院分区：
文献类型：
--
作者：
HARTLEY, SB;COOKE, MP;GOODNOW, CC
在转基因小鼠中，如果自身反应性 B 淋巴细胞在骨髓内发育过程中遇到膜结合的自身抗原，它们就会被消除。我们在这里展示了两个独立且连续的事件（发育停滞和细胞死亡）导致 B 细胞消除。发育停滞是未成熟 B 细胞中抗原结合的早期结果，阻碍了对 B 细胞迁移和激活重要的粘附分子和受体的获得，并且通过去除抗原可以快速逆转。停滞的 B 细胞在 1 至 3 天内死亡，并且可以通过 bcl-2 转基因的表达来延迟，这会导致大量自身反应性 B 细胞从骨髓中逃逸，但无法克服发育停滞。这些发现定义了一种新的 B 细胞消除途径，涉及自身免疫性疾病中容易崩溃的初始阶段。
In transgenic mice, self-reactive B lymphocytes are eliminated if they encounter membrane-bound self antigens during their development within the bone marrow. We show here that two separate and sequential events, arrested development and cell death, bring about B cell elimination. Developmental arrest is an early outcome of antigen binding in immature B cells, blocks acquisition of adhesion molecules and receptors important for B cell migration and activation, and is rapidly reversible by removal of antigen. Death of the arrested B cells occurs within 1 to 3 days and can be delayed by expression of a bcl-2 transgene, which results in escape of large numbers of self-reactive B cells from the bone marrow but fails to override the developmental arrest. These findings define a novel pathway for B cell elimination, involving an initial stage vulnerable to breakdown in autoimmune disease.