Persistent antigen and germinal center B cells sustain T follicular helper cell responses and phenotype.

Abstract

T follicular helper (Tfh) cells provide help to B cells and are crucial for establishment of germinal center (GC) reactions, including production of high-affinity antibodies and generation of memory B cells and long-lived plasma cells. Here we report that the magnitude of the Tfh cell response was dictated by the amount of antigen and directly correlated with the magnitude of the GC B cell response. In addition, maintenance of the Tfh cell phenotype required sustained antigenic stimulation by GC B cells. In lymphopenic conditions, a strong and prolonged Tfh cell response led to bystander B cell activation, hypergammaglobulinemia, and production of poly- and self-reactive antibodies. These data demonstrate that antigen dose determines the size and duration of the Tfh cell response and GC reaction, highlight the transient nature of the Tfh cell phenotype, and suggest a link between overstimulation of Tfh cells and the development of dysregulated humoral immune responses.

• Authors: Dirk Baumjohann, Silvia Preite, Andrea Reboldi, Francesca Ronchi, K Mark Ansel, Antonio Lanzavecchia, Federica Sallusto
• Journal: Immunity (Immunity) Vol. 38 Issue 3 Pg. 596-605 (Mar 21 2013) ISSN: 1097-4180 [Electronic] United States
• PMID: 23499493 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Antibodies
• Antigens
• CD3 Complex
• CD40 Antigens
• CXCR5 protein, mouse
• Cd3e protein, mouse
• Icos protein, mouse
• Icosl protein, mouse
• Inducible T-Cell Co-Stimulator Ligand
• Inducible T-Cell Co-Stimulator Protein
• Luminescent Proteins
• Receptors, CXCR5
• CD40 Ligand
• Ovalbumin

Topics

• Animals
• Antibodies (immunology)
• Antigens (immunology)
• B-Lymphocytes (immunology, metabolism)
• CD3 Complex (genetics, immunology, metabolism)
• CD40 Antigens (immunology, metabolism)
• CD40 Ligand (immunology, metabolism)
• Cell Line, Tumor
• Flow Cytometry
• Germinal Center (immunology, metabolism)
• Humans
• Immunization (methods)
• Immunophenotyping
• Inducible T-Cell Co-Stimulator Ligand (immunology, metabolism)
• Inducible T-Cell Co-Stimulator Protein (immunology, metabolism)
• Luminescent Proteins (genetics, metabolism)
• Lymphocyte Count
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Mice, Transgenic
• Ovalbumin (administration & dosage, immunology)
• Protein Binding (immunology)
• Receptors, CXCR5 (genetics, immunology, metabolism)
• T-Lymphocytes, Helper-Inducer (immunology, metabolism)