Cutting Edge: IL-21 and Tissue-Specific Signals Instruct Tbet+CD11c+ B Cell Development following Viral Infection

Authors

Wenzhi Song
Gina M Sanchez
Daniel P Mayer
Holly N Blackburn
Irene Chernova
Richard A Flavell
Jason S Weinstein
Joe Craft

Publication Date

6-15-2023

Journal

The Journal of Immunology

Abstract

Tbet+CD11c+ B cells, also known as age-associated B cells (ABCs), are pivotal contributors to humoral immunity following infection and in autoimmunity, yet their in vivo generation is incompletely understood. We used a mouse model of systemic acute lymphocytic choriomeningitis virus infection to examine the developmental requirements of ABCs that emerged in the spleen and liver. IL-21 signaling through STAT3 was indispensable for ABC development. In contrast, IFN-γ signaling through STAT1 was required for B cell activation and proliferation. Mice that underwent splenectomy or were deficient in lymphotoxin α generated hepatic ABCs despite the lack of secondary lymphoid organ contributions, suggesting that the liver supported de novo generation of these cells separately from their development in lymphoid organs. Thus, IFN-γ and IL-21 signaling have distinct, stage-specific roles in ABC differentiation, while the tissue microenvironment provides additional cues necessary for their development.

Keywords

Mice, Animals, Mice, Knockout, Interleukins, Lymphocytic Choriomeningitis, Cell Differentiation, Mice, Inbred C57BL

Comments

Supplementary Materials

PMID: 37133336