Cutting Edge: IL-10 Is Essential for the Generation of Germinal Center B Cell Responses and Anti-Plasmodium Humoral Immunity

Jenna J Guthmiller; Amy C Graham; Ryan A Zander; Rosemary L Pope; Noah S Butler

doi:10.4049/jimmunol.1601762

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Cutting Edge: IL-10 Is Essential for the Generation of Germinal Center B Cell Responses and Anti-Plasmodium Humoral Immunity

Journal article

Open access

Peer reviewed

Cutting Edge: IL-10 Is Essential for the Generation of Germinal Center B Cell Responses and Anti-Plasmodium Humoral Immunity

Jenna J Guthmiller, Amy C Graham, Ryan A Zander, Rosemary L Pope and Noah S Butler

The Journal of immunology (1950), Vol.198(2), pp.617-622

01/15/2017

DOI: 10.4049/jimmunol.1601762

PMCID: PMC5225073

PMID: 27940658

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https://doi.org/10.4049/jimmunol.1601762View

Published (Version of record) Open Access

Abstract

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.

Enzyme-Linked Immunosorbent Assay

Antibodies, Protozoan - immunology

Immunity, Humoral - immunology

Germinal Center - immunology

Malaria - immunology

Mice, Inbred C57BL

Plasmodium yoelii

Mice, Knockout

Lymphocyte Activation - immunology

Animals

B-Lymphocytes - immunology

Flow Cytometry

Mice

Interleukin-10 - immunology

Disease Models, Animal

Details

Title: Subtitle: Cutting Edge: IL-10 Is Essential for the Generation of Germinal Center B Cell Responses and Anti-Plasmodium Humoral Immunity
Creators: Jenna J Guthmiller - Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104
Amy C Graham - Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104
Ryan A Zander - Blood Research Institute, Blood Center of Wisconsin, Milwaukee, WI 53213; and
Rosemary L Pope - Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104
Noah S Butler - Graduate Program in Biomedical Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.198(2), pp.617-622
DOI: 10.4049/jimmunol.1601762
PMID: 27940658
PMCID: PMC5225073
NLM abbreviation: J Immunol
ISSN: 1550-6606
eISSN: 1550-6606
Publisher: United States
Grant note: R01 AI127481 / NIAID NIH HHS T32 AI007633 / NIAID NIH HHS R01 AI125446 / NIAID NIH HHS P20 GM103447 / NIGMS NIH HHS
Language: English
Date published: 01/15/2017
Academic Unit: Microbiology and Immunology
Record Identifier: 9984001144802771

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