B cell tolerance has been generally understood to be an acquired property of the immune system that governs antibody specificity in ways that avoid auto-toxicity. As useful as this understanding has proved, it fails to fully explain the existence of auto-reactive specificities in healthy individuals and contribution these may have to health. Mechanisms underlying B cell tolerance are considered to select a clonal repertoire that generates a collection of antibodies that do not bind self, ie tolerance operates more or less in three dimensions that largely spare autologous cells and antigens. Yet, most B lymphocytes in humans and probably in other vertebrates are auto-reactive and absence of these auto-reactive B cells is associated with disease. We suggest that auto-reactivity can be embodied by extending the concept of tolerance by two further dimensions, one of time and circumstance and one that allows healthy cells to actively resist injury. In this novel concept, macromolecular recognition by the B cell receptor leading to deletion, anergy, receptor editing or B cell activation is extended by taking account of the time of development of normal immune responses (4th dimension) and the accommodation (or tolerance) of normal cells to bound antibody, activation of complement, and interaction with inflammatory cells (fifth dimension). We discuss how these dimensions contribute to understanding B cell biology in health or disease.

中文翻译：

---

B 细胞耐受性的五个维度。

B 细胞耐受性通常被认为是免疫系统的一种后天特性，它以避免自身毒性的方式控制抗体特异性。尽管这种理解已被证明是有用的，但它未能完全解释健康个体中自身反应特异性的存在以及这些特异性可能对健康的贡献。B细胞耐受性的机制被认为是选择产生不结合自身的抗体集合的克隆库，即耐受性或多或少地在三个维度上起作用，这很大程度上不影响自体细胞和抗原。然而，人类以及其他脊椎动物中的大多数 B 淋巴细胞都具有自身反应性，并且这些自身反应性 B 细胞的缺乏与疾病有关。我们认为，自身反应性可以通过将耐受性的概念扩展到两个维度来体现，一是时间和环境，二是允许健康细胞主动抵抗损伤。在这个新颖的概念中，通过考虑正常免疫反应（第四维）的发展时间和适应（或耐受性），B细胞受体的大分子识别导致缺失、无反应性、受体编辑或B细胞激活被延长。正常细胞结合抗体、激活补体以及与炎症细胞相互作用（第五维）。我们讨论这些维度如何有助于理解健康或疾病中的 B 细胞生物学。