Treatment of ongoing autoimmune encephalomyelitis with activated B-cell progenitors maturing into regulatory B cells.

Abstract

The influence of signals perceived by immature B cells during their development in bone marrow on their subsequent functions as mature cells are poorly defined. Here, we show that bone marrow cells transiently stimulated in vivo or in vitro through the Toll-like receptor 9 generate proB cells (CpG-proBs) that interrupt experimental autoimmune encephalomyelitis (EAE) when transferred at the onset of clinical symptoms. Protection requires differentiation of CpG-proBs into mature B cells that home to reactive lymph nodes, where they trap T cells by releasing the CCR7 ligand, CCL19, and to inflamed central nervous system, where they locally limit immunopathogenesis through interleukin-10 production, thereby cooperatively inhibiting ongoing EAE. These data demonstrate that a transient inflammation at the environment, where proB cells develop, is sufficient to confer regulatory functions onto their mature B-cell progeny. In addition, these properties of CpG-proBs open interesting perspectives for cell therapy of autoimmune diseases.

• Authors: Sarantis Korniotis, Christophe Gras, Hélène Letscher, Ruddy Montandon, Jérôme Mégret, Stefanie Siegert, Sophie Ezine, Padraic G Fallon, Sanjiv A Luther, Simon Fillatreau, Flora Zavala
• Journal: Nature communications (Nat Commun) Vol. 7 Pg. 12134 (07 11 2016) ISSN: 2041-1723 [Electronic] England
• PMID: 27396388 (Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CPG 10101
• Ccl19 protein, mouse
• Chemokine CCL19
• IL10 protein, mouse
• Oligodeoxyribonucleotides
• Interleukin-10
• Interferon-gamma

Topics

• Animals
• B-Lymphocytes, Regulatory (cytology, physiology)
• Bone Marrow Transplantation
• Cell Differentiation
• Cell Movement
• Chemokine CCL19 (physiology)
• Encephalomyelitis, Autoimmune, Experimental (therapy)
• Female
• Interferon-gamma (metabolism)
• Interleukin-10 (metabolism)
• Lymph Nodes (physiology)
• Mice, Inbred C57BL
• Oligodeoxyribonucleotides
• Precursor Cells, B-Lymphoid (physiology, transplantation)