Journal
IMMUNITY
Volume 53, Issue 3, Pages 548-+Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2020.08.001
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Funding
- NIH NIAID [Al100663, UM1 AI144462]
- NIAID [AI048240]
- US Department of Defense [W911NF-18-2-0048]
- Ragon Institute of MGH, MIT and Harvard
- NIH [S10OD021831, K99 AI145762]
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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.
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