T-bet+ Memory B Cells Link to Local Cross-Reactive IgG upon Human Rhinovirus Infection.

Abstract

Human rhinoviruses cause the common cold and exacerbate chronic respiratory diseases. Although infection elicits neutralizing antibodies, these do not persist or cross-protect across multiple rhinovirus strains. To analyze rhinovirus-specific B cell responses in humans, we developed techniques using intact RV-A16 and RV-A39 for high-throughput high-dimensional single-cell analysis, with parallel assessment of antibody isotypes in an experimental infection model. Our approach identified T-bet+ B cells binding both viruses that account for ∼5% of CXCR5- memory B cells. These B cells infiltrate nasal tissue and expand in the blood after infection. Their rapid secretion of heterotypic immunoglobulin G (IgG) in vitro, but not IgA, matches the nasal antibody profile post-infection. By contrast, CXCR5+ memory B cells binding a single virus are clonally distinct, absent in nasal tissue, and secrete homotypic IgG and IgA, mirroring the systemic response. Temporal and spatial functions of dichotomous memory B cells might explain the ability to resolve infection while rendering the host susceptible to re-infection.

• Authors: Jacob D Eccles, Ronald B Turner, Nicole A Kirk, Lyndsey M Muehling, Larry Borish, John W Steinke, Spencer C Payne, Paul W Wright, Deborah Thacker, Sampo J Lahtinen, Markus J Lehtinen, Peter W Heymann, Judith A Woodfolk
• Journal: Cell reports (Cell Rep) Vol. 30 Issue 2 Pg. 351-366.e7 (01 14 2020) ISSN: 2211-1247 [Electronic] United States
• PMID: 31940481 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Immunoglobulin G

Topics

• B-Lymphocytes (immunology)
• Cross Reactions (immunology)
• Humans
• Immunoglobulin G (immunology)
• Immunologic Memory (immunology)
• Rhinovirus (immunology)