Naive B Cells Generate Regulatory T Cells in the Presence of a Mature Immunologic Synapse.
From: Helmholtz Centre for Infection Research (HZI), Junior Research Group Immunodynamics, Braunschweig, Germany.
Blood
- Publish Date: Sep 2007
- ISSN: 0006-4971
- Volume: 110
- Issue: 5
- Pages: 1519-29
- Medium: Print
- Language: English
- Citation (JAMA): Reichardt Peter, Dornbach Bastian, Rong Song, et al. Naive B Cells Generate Regulatory T Cells in the Presence of a Mature Immunologic Synapse.. Blood Sep 2007;110:1519-29
Abstract
Naive B cells are ineffective antigen-presenting cells and are considered unable to activate naive T cells. However, antigen-specific contact of these cells leads to stable cell pairs that remain associated over hours in vivo. The physiologic role of such pairs has not been evaluated. We show here that antigen-specific conjugates between naive B cells and naive T cells display a mature immunologic synapse in the contact zone that is absent in T-cell-dendritic-cell (DC) pairs. B cells induce substantial proliferation but, contrary to DCs, no loss of L-selectin in T cells. Surprisingly, while DC-triggered T cells develop into normal effector cells, B-cell stimulation over 72 hours induces regulatory T cells inhibiting priming of fresh T cells in a contact-dependent manner in vitro. In vivo, the regulatory T cells home to lymph nodes where they potently suppress immune responses such as in cutaneous hypersensitivity and ectopic allogeneic heart transplant rejection. Our finding might help to explain old observations on tolerance induction by B cells, identify the mature immunologic synapse as a central functional module of this process, and suggest the use of naive B-cell-primed regulatory T cells, “bTregs,” as a useful approach for therapeutic intervention in adverse adaptive immune responses.
Mesh Headings (Keywords): Animals, Antigen Presentation, Antigens, B-Lymphocytes, Cell Communication, Cell Proliferation, Cells, Cultured, Dendritic Cells, Dermatitis, Atopic, Graft Rejection, Heart Transplantation, L-Selectin, Lymph Nodes, Lymphocyte Activation, Mice, Mice, Inbred BALB C, Mice, Transgenic, T-Lymphocytes, Regulatory, Transplantation Tolerance, Transplantation, Homologous
Check for Full Text / PubMed Unique Identifier (PMID): 17392507
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