NDLI: IFN-Î³-producing CD4+ T cells promote generation of protective germinal center-derived IgM+ B cell memory against Salmonella Typhi.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Chai, Qian Lopez-Macias, Constantino Isibasi, Armando Gil-Cruz, Cristina Hisaki, Emiliano Pastelin-Palacios, Rodolfo Waisman, Ari Perez-Shibayama, Christian Onder, Lucas Cervantes-Barragan, Luisa Scandella, Elke Regen, Tommy Ludewig, Burkhard
Description	Author Affiliation: Perez-Shibayama C ( Institute of Immunobiology, Kantonal Hospital St. Gallen, CH-9007 St. Gallen, Switzerland); Gil-Cruz C ( Institute of Immunobiology, Kantonal Hospital St. Gallen, CH-9007 St. Gallen, Switzerland); Pastelin-Palacios R ( Facultad de Química, Universidad Nacional Autónoma de México, Mexico City, C.P. 04510 Mexico); Cervantes-Barragan L ( Institute of Immunobiology, Kantonal Hospital St. Gallen, CH-9007 St. Gallen, Switzerland); Hisaki E ( Medical Research Unit on Immunochemistry, Specialties Hospital, National Medical Centre 'Siglo XXI,' Mexican Social Security Institute, Mexico City, C.P. 06020 Mexico); Chai Q ( Institute of Immunobiology, Kantonal Hospital St. Gallen, CH-9007 St. Gallen, Switzerland); Onder L ( Institute of Immunobiology, Kantonal Hospital St. Gallen, CH-9007 St. Gallen, Switzerland); Scandella E ( Institute of Immunobiology, Kantonal Hospital St. Gallen, CH-9007 St. Gallen, Switzerland); Regen T ( Institute for Molecular Medicine, University of Mainz, D-55131 Mainz, Germany.); Waisman A ( Institute for Molecular Medicine, University of Mainz, D-55131 Mainz, Germany.); Isibasi A ( Medical Research Unit on Immunochemistry, Specialties Hospital, National Medical Centre 'Siglo XXI,' Mexican Social Security Institute, Mexico City, C.P. 06020 Mexico); Lopez-Macias C ( Medical Research Unit on Immunochemistry, Specialties Hospital, National Medical Centre 'Siglo XXI,' Mexican Social Security Institute, Mexico City, C.P. 06020 Mexico); Ludewig B ( Institute of Immunobiology, Kantonal Hospital St. Gallen, CH-9007 St. Gallen, Switzerland)
Abstract	Abs play a significant role in protection against the intracellular bacterium Salmonella Typhi. In this article, we investigated how long-term protective IgM responses can be elicited by a S. Typhi outer-membrane protein C- and F-based subunit vaccine (porins). We found that repeated Ag exposure promoted a CD4(+) T cell-dependent germinal center reaction that generated mutated IgM-producing B cells and was accompanied by a strong expansion of IFN-Î³-secreting T follicular helper cells. Genetic ablation of individual cytokine receptors revealed that both IFN-Î³ and IL-17 are required for optimal germinal center reactions and production of porin-specific memory IgM(+) B cells. However, more profound reduction of porin-specific IgM B cell responses in the absence of IFN-Î³R signaling indicated that this cytokine plays a dominant role. Importantly, mutated IgM mAbs against porins exhibited bactericidal capacity and efficiently augmented S. Typhi clearance. In conclusion, repeated vaccination with S. Typhi porins programs type I T follicular helper cell responses that contribute to the diversification of B cell memory and promote the generation of protective IgM Abs.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	11
Volume Number	192
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2014-06-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	B-lymphocytes Immunology Cd4-positive T-lymphocytes Germinal Center Immunoglobulin M Immunologic Memory Interferon-gamma Salmonella Typhi Animals Pathology Genetics Mice Mice, Knockout Salmonella Vaccines Typhoid Fever Prevention & Control Randomized Controlled Trial Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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