Diverse B cell responses are important for generating antibody‐mediated protection against highly variable pathogens. While some antigens can trigger T‐independent B cell proliferation and short‐term antibody production, development of long‐term humoral immunity requires T‐dependent B cell responses. The “two‐signal” model of B cell activation has long been invoked to explain alternate B cell recruitment into immune response to foreign antigens vs. induction of tolerance to self‐antigens. However, a number of other factors appear to influence the fate of mature B cells responding to antigen in vivo. In this review, we will discuss how various spatiotemporal scenarios of antigen access into secondary lymphoid organs, antigen valency and cellular environment of antigen acquisition by B cells, duration of B cell access to antigen and the timing of T cell help may affect follicular B cell fate, including death, survival, anergy, and recruitment into T‐dependent responses. We will also highlight unresolved questions related to B cell activation and tolerance in vivo that may have important implications for vaccine development and autoimmunity.

中文翻译：

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信号 1、2 和 B 细胞命运或：地点、时间和持续多长时间？

多样化的 B 细胞反应对于产生抗体介导的针对高度可变病原体的保护很重要。虽然一些抗原可以触发 T 依赖性 B 细胞增殖和短期抗体产生，但长期体液免疫的发展需要 T 依赖性 B 细胞反应。B 细胞激活的“双信号”模型长期以来一直被用来解释交替的 B 细胞募集到针对外来抗原的免疫反应与诱导对自身抗原的耐受性。然而，许多其他因素似乎会影响成熟 B 细胞在体内对抗原作出反应的命运。在这篇综述中，我们将讨论抗原进入次级淋巴器官的各种时空情景，B 细胞获取抗原的抗原价和细胞环境，，包括死亡、存活、无反应性和 T 依赖性反应的募集。我们还将强调与体内 B 细胞活化和耐受性相关的未解决问题，这些问题可能对疫苗开发和自身免疫具有重要意义。