Activated B cells participate in either extrafollicular (EF) or germinal center (GC) responses. Canonical responses are composed of a short wave of plasmablasts (PBs) arising from EF sites, followed by GC producing somatically mutated memory B cells (MBC) and long-lived plasma cells. However, somatic hypermutation (SHM) and affinity maturation can take place at both sites, and a substantial fraction of MBC are produced prior to GC formation. Infection responses range from GC responses that persist for months to persistent EF responses with dominant suppression of GCs. Here, we review the current understanding of the functional output of EF and GC responses and the molecular switches promoting them. We discuss the signals that regulate the magnitude and duration of these responses, and outline gaps in knowledge and important areas of inquiry. Understanding such molecular switches will be critical for vaccine development, interpretation of vaccine efficacy and the treatment for autoimmune diseases.

活化的 B 细胞参与滤泡外 (EF) 或生发中心 (GC) 反应。典型反应由来自 EF 位点的短波浆母细胞 (PB) 组成，然后是产生体细胞突变记忆 B 细胞 (MBC) 和长寿命浆细胞的 GC。然而，体细胞超突变 (SHM) 和亲和力成熟可以在两个位点发生，并且大部分 MBC 是在 GC 形成之前产生的。感染反应范围从持续数月的 GC 反应到显性抑制 GC 的持续 EF 反应。在这里，我们回顾了当前对 EF 和 GC 响应的功能输出以及促进它们的分子开关的理解。我们讨论了调节这些反应的幅度和持续时间的信号，并概述了知识和重要调查领域的差距。