Multifaceted Effects of Antigen Valency on B Cell Response Composition and Differentiation In Vivo

Summary

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.

Highlights

• Detailed mechanistic understanding of how differing antigen valencies influence cognate B cells in vivo is lacking.
• Antigen valency dictates the magnitude and composition of B cell responses.
• High valency enables robust activation and effector differentiation of B cells.
• Kato et al. show antigen valency dictates the breadth of affinity range of B cells that are recruited and the ability of cognate B cells to differentiate into effector cells.
• This had profound impacts on the magnitude of germinal center and extrafollicular plasmablast responses. The study also highlights the need to carefully consider valency in vaccine design.