B Lymphocytes Are Required during the Early Priming of CD4⁺ T Cells for Clearance of Pneumocystis Infection in Mice

Authors

Michael M. Opata, University of Kentucky
Melissa L. Hollifield, University of KentuckyFollow
Frances E. Lund, University of Alabama at Birmingham
Troy D. Randall, University of Alabama at Birmingham
Robert Dunn, Novartis Research Foundation
Beth A. Garvy, University of KentuckyFollow
David J. Feola, University of KentuckyFollow

Abstract

B cells play a critical role in the clearance of Pneumocystis. In addition to production of Pneumocystis-specific Abs, B cells are required during the priming phase for CD4⁺ T cells to expand normally and generate memory. Clearance of Pneumocystis was found to be dependent on Ag specific B cells and on the ability of B cells to secrete Pneumocystis-specific Ab, as mice with B cells defective in these functions or with a restricted BCR were unable to control Pneumocystis infection. Because Pneumocystis-specific antiserum was only able to partially protect B cell–deficient mice from infection, we hypothesized that optimal T cell priming requires fully functional B cells. Using adoptive transfer and B cell depletion strategies, we determined that optimal priming of CD4⁺ T cells requires B cells during the first 2–3 d of infection and that this was independent of the production of Ab. T cells that were removed from Pneumocystis-infected mice during the priming phase were fully functional and able to clear Pneumocystis infection upon adoptive transfer into Rag1^−/− hosts, but this effect was ablated in mice that lacked fully functional B cells. Our results indicate that T cell priming requires a complete environment of Ag presentation and activation signals to become fully functional in this model of Pneumocystis infection.

Document Type

Article

Publication Date

7-15-2015

Notes/Citation Information

Published in The Journal of Immunology, v. 195, no. 2, p. 611-620.

Copyright © 2015 by The American Association of Immunologists, Inc.

The copyright holder has granted the permission for posting the article here.

The document available for download is the authors' post-peer-review final draft of the article.

Digital Object Identifier (DOI)

https://doi.org/10.4049/jimmunol.1500112

Funding Information

This work was supported by National Institutes of Health/National Heart, Lung, and Blood Institute Grant HL088989 (to B.A.G.).

Related Content

The online version of this article contains supplemental material.

Repository Citation

Opata, Michael M.; Hollifield, Melissa L.; Lund, Frances E.; Randall, Troy D.; Dunn, Robert; Garvy, Beth A.; and Feola, David J., "B Lymphocytes Are Required during the Early Priming of CD4⁺ T Cells for Clearance of Pneumocystis Infection in Mice" (2015). Microbiology, Immunology, and Molecular Genetics Faculty Publications. 145.
https://uknowledge.uky.edu/microbio_facpub/145