ZBTB32 restrains antibody responses to murine cytomegalovirus infections, but not other repetitive challenges
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Author
Jash, ArijitaZhou, You W
Gerardo, Diana K
Ripperger, Tyler J
Parikh, Bijal A
Piersma, Sytse
Jamwal, Deepa R
Kiela, Pawel R
Boon, Adrianus C M
Yokoyama, Wayne M
Hsieh, Chyi S
Bhattacharya, Deepta
Affiliation
Univ Arizona, Coll Med, Dept ImmunobiolUniv Arizona, Coll Med, Dept Pediat
Issue Date
2019-10-24
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NATURE PUBLISHING GROUPCitation
Jash, A., Zhou, Y.W., Gerardo, D.K. et al. ZBTB32 restrains antibody responses to murine cytomegalovirus infections, but not other repetitive challenges. Sci Rep 9, 15257 (2019) doi:10.1038/s41598-019-51860-zJournal
SCIENTIFIC REPORTSRights
Copyright © The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Collection Information
This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.Abstract
ZBTB32 is a transcription factor that is highly expressed by a subset of memory B cells and restrains the magnitude and duration of recall responses against hapten-protein conjugates. To define physiological contexts in which ZBTB32 acts, we assessed responses by Zbtb32-/- mice or bone marrow chimeras against a panel of chronic and acute challenges. Mixed bone marrow chimeras were established in which all B cells were derived from either Zbtb32-/- mice or control littermates. Chronic infection of Zbtb32-/- chimeras with murine cytomegalovirus led to nearly 20-fold higher antigen-specific IgG2b levels relative to controls by week 9 post-infection, despite similar viral loads. In contrast, IgA responses and specificities in the intestine, where memory B cells are repeatedly stimulated by commensal bacteria, were similar between Zbtb32-/- mice and control littermates. Finally, an infection and heterologous booster vaccination model revealed no role for ZBTB32 in restraining primary or recall antibody responses against influenza viruses. Thus, ZBTB32 does not limit recall responses to a number of physiological acute challenges, but does restrict antibody levels during chronic viral infections that periodically engage memory B cells. This restriction might selectively prevent recall responses against chronic infections from progressively overwhelming other antibody specificities.Note
Open access journalISSN
2045-2322PubMed ID
31649328Version
Final published versionSponsors
National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01AI99109, R01AI131680, U01AI131349, K08AI04991]; New York Stem Cell Foundationae974a485f413a2113503eed53cd6c53
10.1038/s41598-019-51860-z