1. Multifaceted Effects of Antigen Valency on B Cell Response Composition and Differentiation In Vivo.
- Author
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Kato Y, Abbott RK, Freeman BL, Haupt S, Groschel B, Silva M, Menis S, Irvine DJ, Schief WR, and Crotty S
- Subjects
- Animals, CD4-Positive T-Lymphocytes immunology, Cell Differentiation immunology, Cell Proliferation physiology, Interferon Regulatory Factors immunology, Lymphocyte Activation immunology, Mice, Mice, Inbred C57BL, Plasma Cells immunology, Protein Multimerization immunology, Proto-Oncogene Proteins c-bcl-6 immunology, Antibody Affinity immunology, Antigens immunology, B-Lymphocytes immunology, Binding Sites, Antibody immunology, Germinal Center immunology
- Abstract
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., Competing Interests: Declaration of Interests S.M. and W.R.S. are inventors on patent applications filed by IAVI and Scripps on eOD-GT8 60-mer., (Copyright © 2020 Elsevier Inc. All rights reserved.)- Published
- 2020
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