Direct tolerance induction in mature B lymphocytes may resemble clonal anergy phenomenon.
Direct tolerance induction in mature B lymphocytes may resemble clonal anergy phenomenon.
复制标题
成熟 B 淋巴细胞中的直接耐受诱导可能类似于克隆无反应现象。
DOI：
10.1007/bf02918169
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发表时间：
1991
影响因子：
4.4
通讯作者：
Pratt,L
中科院分区：
文献类型：
--
作者：
Aldo-Benson,M;Pratt,L
已经提出了几种机制用于在成熟B细胞中直接诱导B细胞耐受，例如Bretscher和Cohn [5]假说，该假说指出，针对B细胞的抗原信号在没有T细胞或淋巴因子提供的“第二信号”的情况下产生无应答性。第二种解释是交联免疫球蛋白和Fc受体的耐受原通过磷脂酰肌醇途径中止B细胞的生化活化。我们的研究结果与这两种假设都不一致。我们推测DNP-MGG诱导成熟B细胞中的免疫球蛋白受体加帽和内化，但是当DNP-MGG以类似于克隆无反应性的方式存在于抗原受体再表达时，抑制信号被给予B细胞。本文报道的研究验证了这一假设作为直接B细胞耐受的一个可能的额外机制。当纯DNP特异性B细胞与富含淋巴因子的EL-4上清液中的DNP-MGG孵育6小时时，诱导了免疫应答：但与DNP-MGG在淋巴因子存在下预孵育48小时诱导了耐受。如果将B细胞培养物与DNP-MGG预孵育6小时，然后在没有缀合物的情况下孵育24小时，然后加入DNP-MGG进行第三个18小时的预新生期（此时受体正在重新表达），则诱导耐受性。在第一或第三时间段中用DNP-Ficoll抗原替代DNP-MGG未导致耐受诱导，但在这两个时间段中的任一时间段中替代DNP-KLH确实导致耐受。
Several mechanisms have been postulated for direct induction of B-cell tolerance in mature B cells, such as the Bretscher and Cohn [5] hypothesis which states that an antigenic signal to B cells without the ‘second signal’ provided by T cells or lymphokines produces unresponsiveness. A second explanation is that tolerogens which cross-link immunoglobulin and Fc receptors abort the biochemical activation of the B cell via the phosphatidyl inositol pathway. Results of our studies are not consistent with either of these hypotheses. We speculated that DNP-MGG induces immunoglobulin receptor capping and internalization in mature B cells, but a suppressive signal is given to the B cell when DNP-MGG is present at the time of antigen receptor reexpression in a fashion similar to clonal anergy. The studies reported here test this hypothesis as a possible additional mechanism of direct B-cell tolerance.When pure DNP-specific B cells were incubated for 6 h with DNP-MGG in the presence of lymphokine-rich EL-4 supernatant, an immune response was induced: but 48 h preincubation with DNP-MGG in the presence of lymphokines induced tolerance. If B-cell cultures were preincubated with DNP-MGG for 6 h followed by a 24-hour incubation without conjugate and DNP-MGG was then added for the third preineubation period of 18 h (at a time when receptors are being reexpressed), tolerance was induced. Substitution of DNP-Ficoll antigen for DNP-MGG in either the first or third time period did not result in tolerance induction but substituting DNP-KLH during either of these two periods did result in tolerance.