Gauld Stephen B, Benschop Robert J, Merrell Kevin T, Cambier John C
Integrated Department of Immunology, University of Colorado Health Sciences Center and National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
Nat Immunol. 2005 Nov;6(11):1160-7. doi: 10.1038/ni1256. Epub 2005 Oct 2.
Immunological tolerance can be mediated by anergy, in which self-reactive B cells persist in the periphery yet remain unresponsive to immunogen. Whether anergy is induced after transient exposure to self antigen and is 'remembered' or requires continuous antigen receptor occupancy and transduction of signals remains unclear. We have explored this using an immunoglobulin-transgenic mouse in which B cells were hapten specific (arsonate) yet cross-reacted with a self antigen that induced anergy in vivo. Many features of anergic cells were rapidly reversed after dissociation of self antigen using hapten competition and these cells regained antigen responsiveness. Our findings indicate that continuous binding of antigen and subsequent receptor signaling are essential for the maintenance of anergy.
免疫耐受可由无反应性介导，其中自身反应性B细胞在外周持续存在，但对免疫原仍无反应。无反应性是在短暂接触自身抗原后诱导产生并被“记忆”，还是需要持续的抗原受体占据和信号转导，目前尚不清楚。我们使用一种免疫球蛋白转基因小鼠对此进行了探究，在这种小鼠中，B细胞对半抗原具有特异性（砷酸盐），但与一种在体内诱导无反应性的自身抗原发生交叉反应。使用半抗原竞争使自身抗原解离后，无反应性细胞的许多特征迅速逆转，这些细胞恢复了抗原反应性。我们的研究结果表明，抗原的持续结合和随后的受体信号传导对于维持无反应性至关重要。
