B-1a lymphocytes promote oligodendrogenesis during brain development

Shogo Tanabe; Toshihide Yamashita

doi:10.1038/s41593-018-0106-4

B-1a lymphocytes promote oligodendrogenesis during brain development

Nat Neurosci. 2018 Apr;21(4):506-516. doi: 10.1038/s41593-018-0106-4. Epub 2018 Mar 5.

Authors

Shogo Tanabe¹, Toshihide Yamashita^{2

3

4}

Affiliations

¹ World Premier International Immunology Frontier Research Center, Osaka University, Osaka, Japan.
² World Premier International Immunology Frontier Research Center, Osaka University, Osaka, Japan. yamashita@molneu.med.osaka-u.ac.jp.
³ Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, Osaka, Japan. yamashita@molneu.med.osaka-u.ac.jp.
⁴ Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan. yamashita@molneu.med.osaka-u.ac.jp.

PMID: 29507409
DOI: 10.1038/s41593-018-0106-4

Abstract

During brain development, the immune system mediates neurogenesis, gliogenesis and synapse formation. However, it remains unclear whether peripheral lymphocytes contribute to brain development. Here we identified the subtypes of lymphocytes that are present in neonatal mouse brains and investigated their functions. We found that B-1a cells, a subtype of B cells, were abundant in the neonatal mouse brain and infiltrated into the brain in a CXCL13-CXCR5-dependent manner. B-1a cells promoted the proliferation of oligodendrocyte-precursor cells (OPCs) in vitro, and depletion of B-1a cells from developing brains resulted in a reduction of numbers of OPCs and mature oligodendrocytes. Furthermore, neutralizing Fcα/μR, the receptor for the Fc region of IgM secreted by B-1a cells, inhibited OPC proliferation and reduced the proportion of myelinated axons in neonatal mouse brains. Our results demonstrate that B-1a cells infiltrate into the brain and contribute to oligodendrogenesis and myelination by promoting OPC proliferation via IgM-Fcα/μR signaling.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Animals, Newborn
Antibodies / pharmacology
B-Lymphocytes / drug effects
B-Lymphocytes / physiology*
Brain / cytology*
Brain / growth & development*
Brain / immunology
Cell Differentiation
Coculture Techniques
Cytokines / genetics
Cytokines / immunology
Cytokines / metabolism
Embryo, Mammalian
Homeobox Protein Nkx-2.2
Homeodomain Proteins / immunology
Homeodomain Proteins / metabolism
Ki-67 Antigen / metabolism
Mice
Mice, Inbred C57BL
Mice, Transgenic
Nerve Tissue Proteins / metabolism
Neurogenesis
Neutrophil Infiltration / drug effects
Neutrophil Infiltration / physiology
Oligodendrocyte Precursor Cells / drug effects
Oligodendrocyte Precursor Cells / metabolism
Oligodendrocyte Precursor Cells / physiology*
Oligodendroglia / drug effects
Oligodendroglia / physiology*
Oligodendroglia / ultrastructure
Receptor, Platelet-Derived Growth Factor alpha / metabolism
Zebrafish Proteins / immunology
Zebrafish Proteins / metabolism

Substances

Antibodies
Cytokines
Homeobox Protein Nkx-2.2
Homeodomain Proteins
Ki-67 Antigen
Nerve Tissue Proteins
Zebrafish Proteins
Receptor, Platelet-Derived Growth Factor alpha