Gauld Stephen B, Merrell Kevin T, Cambier John C
Integrated Department of Immunology, University of Colorado Health Science Center and National Jewish Medical Research Center, 1400 Jackson Street, Denver, CO 80206, USA.
Curr Opin Immunol. 2006 Jun;18(3):292-7. doi: 10.1016/j.coi.2006.03.015. Epub 2006 Apr 17.
B-cell antigen receptor (BCR) signals are crucial for initiation of humoral immune responses and must be actively modulated and/or terminated in preparation for receipt of subsequent cues for progression. BCR signaling is also actively inhibited in autoreactive cells in which unresponsiveness is maintained by anergy. This serves to prevent cell activation and autoimmunity. Importantly, the feedback mechanisms that modulate and/or terminate signaling during normal antigen-induced B-cell activation appear to also be involved in maintaining B-cell anergy. In fact, it is suggested that anergy reflects nothing more than the normal inability of cells to respond to antigen following preceding stimulation of normal inhibitory feedback mechanisms. Thus, the time-honored two-signal hypothesis is almost certainly correct, with second signals being required to release the cell from inhibitory BCR-specific and trans-active feedback regulation.
B细胞抗原受体（BCR）信号对于启动体液免疫反应至关重要，并且在准备接收后续进展信号时必须被积极调节和/或终止。在自身反应性细胞中，BCR信号也受到积极抑制，其中无反应性通过失能得以维持。这有助于防止细胞活化和自身免疫。重要的是，在正常抗原诱导的B细胞活化过程中调节和/或终止信号的反馈机制似乎也参与维持B细胞失能。事实上，有人提出失能仅仅反映了细胞在先前正常抑制性反馈机制刺激后对抗原作出反应的正常无能。因此，历史悠久的双信号假说几乎肯定是正确的，需要第二信号来使细胞从抑制性BCR特异性和反式激活反馈调节中释放出来。
