Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA; Scripps Consortium for HIV/AIDS Vaccine Development (CHAVD), La Jolla, CA 92037, USA.
Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA.
Immunity. 2020 Sep 15;53(3):548-563.e8. doi: 10.1016/j.immuni.2020.08.001. Epub 2020 Aug 27.
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.
抗原价态如何影响免疫应答过程中的 B 细胞尚不清楚。在此,我们使用具有 1 至 60 种确定价态的 HIV 免疫原,研究了抗原价态在体内 B 细胞应答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种型 B 细胞,而对亲和力的区分很小。这导致早期强烈诱导转录因子 IRF4(干扰素调节因子 4)和 Bcl6,以 CD4 T 细胞依赖性方式驱动早期滤泡外浆细胞和生发中心反应,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,优先招募高亲和力的 B 细胞。因此,抗原价态对 B 细胞反应有多种影响,并可以决定体内 B 细胞的亲和力阈值和竞争格局,对疫苗设计具有重要意义。
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