How antigen valency affects B cells in vivo during immune responses is not well understood. Here, using HIV immunogens with defined valencies ranging from 1 to 60, we investigated the role of antigen valency during different phases of B cell responses in vivo. Highly multimerized immunogens preferentially rapidly activated cognate B cells, with little affinity discrimination. This led to strong early induction of the transcription factors IRF4 (interferon regulatory factor 4) and Bcl6, driving both early extrafollicular plasma cell and germinal center responses, in a CD4⁺ T-cell-dependent manner, involving B cells with a broad range of affinities. Low-valency antigens induced smaller effector B cell responses, with preferential recruitment of high-affinity B cells. Thus, antigen valency has multifaceted effects on B cell responses and can dictate affinity thresholds and competitive landscapes for B cells in vivo, with implications for vaccine design.

在免疫反应过程中，抗原效价如何影响体内的 B 细胞尚不清楚。在这里，我们使用具有从 1 到 60 的确定化合价的 HIV 免疫原，研究了抗原化合价在体内B 细胞反应的不同阶段中的作用。高度多聚化的免疫原优先快速激活同源 B 细胞，几乎没有亲和力歧视。这导致转录因子 IRF4（干扰素调节因子 4）和 Bcl6 的强烈早期诱导，驱动早期滤泡外浆细胞和生发中心反应，在 CD4 ⁺T 细胞依赖性方式，涉及具有广泛亲和力的 B 细胞。低价抗原诱导较小的效应 B 细胞反应，优先募集高亲和力 B 细胞。因此，抗原效价对 B 细胞反应具有多方面的影响，并且可以决定 B 细胞在体内的亲和力阈值和竞争格局，这对疫苗设计有影响。