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Re-utilization of germinal centers in multiple Peyer's patches results in highly synchronized, oligoclonal, and affinity-matured gut IgA responses.

Journal article
Authors Peter Bergqvist
Anneli Stensson
L Hazanov
Anna Holmberg
Johan Mattsson
R Mehr
Mats Bemark
Nils Y Lycke
Published in Mucosal immunology
Volume 6
Pages 122–135
ISSN 1935-3456
Publication year 2013
Published at Institute of Biomedicine, Department of Microbiology and Immunology
Pages 122–135
Language en
Links dx.doi.org/10.1038/mi.2012.56
Subject categories Immunobiology

Abstract

Whereas gut IgA responses to the microbiota may be multi-centered and diverse, little is known about IgA responses to T-cell-dependent antigens following oral immunizations. Using a novel approach, gut IgA responses to oral hapten (4-hydroxy-3-nitrophenyl)acetyl-cholera toxin (NP-CT) conjugates were followed at the cellular and molecular level. Surprisingly, these responses were highly synchronized, strongly oligoclonal, and dominated by affinity matured cells. Extensive lineage trees revealed clonal relationships between NP-specific IgA cells in gut inductive and effector sites, suggesting expansion of the same B-cell clone in multiple Peyer's patches (PPs). Adoptive transfer experiments showed that this was achieved through re-utilization of already existing germinal centers (GCs) in multiple PPs by previously activated GC GL7(+) B cells, provided oral NP-CT was given before cell transfer. Taken together, these results explain why repeated oral immunizations are mandatory for an effective oral vaccine.Mucosal Immunology advance online publication 11 July 2012. doi:10.1038/mi.2012.56.

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