B-Cell-Intrinsic Type 1 Interferon Signaling Is Crucial for Loss of Tolerance and the Development of Autoreactive B Cells

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2018 Jul 12

PMID 29996101

Citations 51

Authors

Phillip P Domeier

Sathi Babu Chodisetti

Stephanie L Schell

Yuka Imamura Kawasawa

Melinda J Fasnacht

Chetna Soni

Ziaur S M Rahman

Affiliations

Soon will be listed here.

Abstract

Type 1 interferon (T1IFN) signaling promotes inflammation and lupus pathology, but its role in autoreactive B cell development in the antibody-forming cell (AFC) and germinal center (GC) pathways is unclear. Using a lupus model that allows for focused study of the AFC and GC responses, we show that T1IFN signaling is crucial for autoreactive B cell development in the AFC and GC pathways. Through bone marrow chimeras, DNA-reactive B cell transfer, and GC-specific Cre mice, we confirm that IFNαR signaling in B cells promotes autoreactive B cell development into both pathways. Transcriptomic analysis reveals gene expression alterations in multiple signaling pathways in non-GC and GC B cells in the absence of IFNαR. Finally, we find that T1IFN signaling promotes autoreactive B cell development in the AFC and GC pathways by regulating BCR signaling. These data suggest value for anti-IFNαR therapy in individuals with elevated T1IFN activity before clinical disease onset.

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