Upon activation, B cells undergo either the germinal center (GC) or extrafollicular (EF) response. While GC are known to generate high-affinity memory B cells and long-lived plasma cells, the role of the EF response is less well understood. Initially, it was thought to be limited to that of a source of fast but lower-quality antibodies until the GC can form. However, recent evidence strongly supports the EF response as an important component of the humoral response to infection. EF responses are now also recognized as a source of pathogenic B cells in autoimmune diseases. The EF response itself is dynamic and regulated by pathways that are only recently being uncovered. We have identified that the cytokine IL-12 acts as a molecular switch, enhancing the EF response and suppressing GC through multiple mechanisms. These include direct effects on both B cells themselves and the coordinated differentiation of helper CD4 T cells. Here, we explore this pathway in relation to other recent advancements in our understanding of the EF response's role and highlight areas for future research. A better understanding of how the EF response forms and is regulated is essential for advancing treatments for many disease states.

Keywords: B cell; IL‐12; autoimmunity; extrafollicular; germinal center; infection.

© 2025 The Author(s). Immunological Reviews published by John Wiley & Sons Ltd.

激活后，B细胞会经历生发中心（GC）或额外follicular（EF）反应。虽然已知生发中心能够生成高亲和力的记忆B细胞和长寿浆细胞，但EF反应的作用尚不完全清楚。最初认为它仅限于在生发中心形成之前作为快速但质量较低的抗体来源。然而，最近的证据强烈支持了EF反应是感染免疫应答中的一个重要组成部分。现在也认识到EF反应是自身免疫疾病中病理性B细胞的一个来源。EF反应本身具有动态性，并受一些最近才开始被发现的途径调节。我们已确定细胞因子IL-12作为分子开关，通过多种机制增强EF反应并抑制GC。这些机制包括对B细胞本身的直接影响以及辅助CD4 T细胞协调分化的调控作用。在这里，我们将探讨该通路与其他近期关于EF反应作用的理解进展，并强调未来研究的方向。更好地理解EF反应的形成和调节对于推进许多疾病状态的治疗方法至关重要。

关键词：B细胞；IL-12；自身免疫；额外follicular；生发中心；感染。