Efficient mechanisms of central tolerance, including receptor editing and deletion, prevent highly self-reactive B cell receptors (BCRs) from populating the periphery. Despite this, modest self-reactivity persists in (and may even be actively selected into) the mature B cell repertoire. In this review, we discuss new insights into mechanisms of peripheral B cell tolerance that restrain mature B cells from mounting inappropriate responses to endogenous antigens, and place recent work into historical context. In particular, we discuss new findings that have arisen from application of a novel in vivo reporter of BCR signaling, Nur77-eGFP, expression of which scales with the degree of self-reactivity in both monoclonal and polyclonal B cell repertoires. We discuss new and historical evidence that self-reactivity is not just tolerated, but actively selected into the peripheral repertoire. We review recent progress in understanding how dual expression of the IgM and IgD BCR isotypes on mature naive follicular B cells tunes responsiveness to endogenous antigen recognition, and discuss how this may be integrated with other features of clonal anergy. Finally, we discuss how expression of Nur77 itself couples chronic antigen stimulation with B cell tolerance.

中文翻译：

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频谱上的自我反应性：外周B细胞耐受性的滑动标度。

包括受体编辑和缺失在内的有效的中枢耐受机制可防止高度自我反应的B细胞受体（BCR）遍布周围。尽管如此，适度的自我反应仍然存在于成熟的B细胞库中（甚至可能被主动选择）。在这篇综述中，我们讨论了对外周B细胞耐受机制的新见解，该机制可抑制成熟B细胞对内源性抗原产生不适当的反应，并将最新工作纳入历史背景。特别是，我们讨论了BCR信号的新型体内报道基因Nur77-eGFP的应用所产生的新发现，该报道的表达随单克隆和多克隆B细胞谱中的自身反应程度而定。我们讨论了新的和历史性的证据，表明自我反应并不仅仅是被容忍的，但积极地选择进入周边剧目。我们回顾了最新的进展，了解在成熟的幼稚卵泡B细胞上IgM和IgD BCR同种型的双重表达如何调节对内源性抗原识别的响应能力，并讨论了它如何与克隆性无反应性的其他特征整合。最后，我们讨论了Nur77本身的表达如何将慢性抗原刺激与B细胞耐受性结合在一起。