Interleukin-10 Mediated Autoregulation of Murine B-1 B-Cells and Its Role in Borrelia hermsii Infection

Authors

Vishal Sindhava, University of Kentucky
Michael E Woodman, University of Kentucky
Brian Stevenson, University of KentuckyFollow
Subbarao Bondada, University of KentuckyFollow

Abstract

B cells are typically characterized as positive regulators of the immune response, primarily by producing antibodies. However, recent studies indicate that various subsets of B cells can perform regulatory functions mainly through IL-10 secretion. Here we discovered that peritoneal B-1 (B-1P) cells produce high levels of IL-10 upon stimulation with several Toll-like receptor (TLR) ligands. High levels of IL-10 suppressed B-1P cell proliferation and differentiation response to all TLR ligands studied in an autocrine manner in vitro and in vivo. IL-10 that accumulated in cultures inhibited B-1P cells at second and subsequent cell divisions mainly at the G1/S interphase. IL-10 inhibits TLR induced B-1P cell activation by blocking the classical NF-kappaB pathway. Co-stimulation with CD40 or BAFF abrogated the IL-10 inhibitory effect on B-1P cells during TLR stimulation. Finally, B-1P cells adoptively transferred from the peritoneal cavity of IL-10^-/- mice showed better clearance of Borrelia hermsii than wild-type B-1P cells. This study described a novel autoregulatory property of B-1P cells mediated by B-1P cell derived IL-10, which may affect the function of B-1P cells in infection and autoimmunity.

Document Type

Article

Publication Date

7-6-2010

Notes/Citation Information

Published in PLoS One, v. 5, issue 7, e11445, p. 1-17.

© 2010 Sindhava et al.

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Digital Object Identifier (DOI)

https://doi.org/10.1371/journal.pone.0011445

Funding Information

These studies were funded by National Institutes of Health (NIH) grants CA09357, AI076956 and funds from the vice president for research at the University of Kentucky to S. Bondada and exploratory funds from the University of Kentucky College of Medicine to Brian Stevenson.

Repository Citation

Sindhava, Vishal; Woodman, Michael E; Stevenson, Brian; and Bondada, Subbarao, "Interleukin-10 Mediated Autoregulation of Murine B-1 B-Cells and Its Role in Borrelia hermsii Infection" (2010). Microbiology, Immunology, and Molecular Genetics Faculty Publications. 1.
https://uknowledge.uky.edu/microbio_facpub/1