IL-10 is a pleiotropic cytokine expressed during malaria, a disease characterized by short-lived, parasite-specific Ab responses. The role of IL-10 in regulating B cell responses during malaria is not known. In this study we report that IL-10 is essential for anti-Plasmodium humoral immunity. We identify that germinal center (GC) B cell reactions, isotype-switched Ab responses, parasite control, and host survival require B cell-intrinsic IL-10 signaling. IL-10 also indirectly supports humoral immunity by suppressing excessive IFN-γ, which induces T-bet expression in B cells. Genetic ablation of either IFN-γ signaling or T-bet expression in B cells substantially enhanced GC B cell responses and anti-Plasmodium Ab production. Together, our data show that B cell-intrinsic IL-10 enhances whereas B cell-intrinsic IFN-γ and T-bet suppress GC B cell responses and anti-Plasmodium humoral immunity. These data identify critical immunoregulatory circuits in B cells that may be targeted to promote long-lived humoral immunity and resistance to malaria.
This work was supported by grants from the American Heart Association (16PRE27660002 to J.J.G.), the National Institutes of Health/National Institute of Allergy and Infectious Diseases (T32AI007633 to R.A.Z.; R01AI125446 and R01AI127481 to N.S.B.), and the National Institutes of Health/National Institute of General Medical Sciences under Grant 8P20GM103447.
The online version of this article contains supplemental material.
Abbreviations used in this article:
- germinal center
- rat γ Ig
- wild type.
- Received October 19, 2016.
- Accepted November 8, 2016.
- Copyright © 2017 by The American Association of Immunologists, Inc.