B cell receptor induced IL-10 production from neonatal mouse CD19+CD43- cells depends on STAT5 mediated IL-6 secretion

Abstract
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Abstract

Newborns are unable to reach the adult-level humoral immune response partly due to the potent immunoregulatory role of IL-10. Increased IL-10 production by neonatal B cells has been attributed to the larger population of IL-10-producting CD43⁺ B-1 cells in neonates. Here, we show that neonatal mouse CD43^- non-B-1 cells also produce substantial amounts of IL-10 following B cell antigen receptor (BCR) activation. In neonatal mouse CD43^- non-B-1 cells, BCR engagement activated STAT5 under the control of phosphorylated forms of signaling molecules Syk, Btk, PKC, FAK and Rac1. Neonatal STAT5 activation led to IL-6 production, which in turn was responsible for IL-10 production in an autocrine/paracrine fashion through the activation of STAT3. In addition to the increased IL-6 production in response to BCR stimulation, elevated expression of IL-6Rα expression in neonatal B cells rendered them highly susceptible to IL-6 mediated STAT3 phosphorylation and IL-10 production. Finally, IL-10 secreted from neonatal mouse CD43^- non-B-1 cells was sufficient to inhibit TNF-α secretion by macrophages. Our results unveil a distinct mechanism of IL-6-dependent IL-10 production in BCR-stimulated neonatal CD19⁺CD43^- B cells.

Data availability

Sequencing data have been deposited in GEO under accession code GSE200955

The following data sets were generated

1. Sakai J
2. Chou C
3. Wu WW
4. Akkoyunlu M
(2022) Next Generation Sequencing analysis of BCR-induced gene expression in adult and neonatal splenic B cells
NCBI Gene Expression Omnibus, GSE200955.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE200955

Article and author information

Author details

Jiro Sakai

Laboratory of Bacterial Polysaccharides, United States Food and Drug Administration, Silver Spring, United States

Competing interests
The authors declare that no competing interests exist.
Jiyeon Yang

Laboratory of Bacterial Polysaccharides, United States Food and Drug Administration, Silver Spring, United States

Competing interests
The authors declare that no competing interests exist.
Chao-Kai Chou

Facility for Biotechnology Resources, United States Food and Drug Administration, Silver Spring, United States

Competing interests
The authors declare that no competing interests exist.
Wells W Wu

Facility for Biotechnology Resources, United States Food and Drug Administration, Silver Spring, United States

Competing interests
The authors declare that no competing interests exist.
Mustafa Akkoyunlu

Laboratory of Bacterial Polysaccharides, United States Food and Drug Administration, Silver Spring, United States

For correspondence
Mustafa.Akkoyunlu@fda.hhs.gov

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-9958-4031

Funding

No external funding was received for this work.

Ethics

Animal experimentation: The mouse experiments described in this study were performed in accordance with the US Food and Drug Administration/Center for Biologics Evaluation and Research Institutional Animal Care and Use Committee guidelines (permit 2002-31 and 2017-45).

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.