Re-utilization of germinal centers in multiple Peyer's patches results in highly synchronized, oligoclonal, and affinity-matured gut IgA responses
Bergqvist, P. ; Stensson, A. ; Hazanov, L. ; Holmberg, A. ; Mattsson, J. ; Mehr, R. ; Bemark, M. LU
and Lycke, N. Y.
(2013)
In Mucosal Immunology
6(1).
p.122-135
- 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... (More)
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.
(Less)
- author
- Bergqvist, P.
; Stensson, A.
; Hazanov, L.
; Holmberg, A.
; Mattsson, J.
; Mehr, R.
; Bemark, M.
LU
and Lycke, N. Y.
- publishing date
- 2013-01
- type
- Contribution to journal
- publication status
- published
- in
- Mucosal Immunology
- volume
- 6
- issue
- 1
- pages
- 14 pages
- publisher
- Nature Publishing Group
- external identifiers
-
- pmid:22785230
- scopus:84864331772
- ISSN
- 1933-0219
- DOI
- 10.1038/mi.2012.56
- language
- English
- LU publication?
- no
- id
- c72f76eb-67eb-4f06-9b67-e6a087cd11ba
- date added to LUP
- 2023-12-06 16:46:41
- date last changed
- 2024-05-31 15:48:20
@article{c72f76eb-67eb-4f06-9b67-e6a087cd11ba,
abstract = {{<p>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 <sup>+</sup> 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.</p>}},
author = {{Bergqvist, P. and Stensson, A. and Hazanov, L. and Holmberg, A. and Mattsson, J. and Mehr, R. and Bemark, M. and Lycke, N. Y.}},
issn = {{1933-0219}},
language = {{eng}},
number = {{1}},
pages = {{122--135}},
publisher = {{Nature Publishing Group}},
series = {{Mucosal Immunology}},
title = {{Re-utilization of germinal centers in multiple Peyer's patches results in highly synchronized, oligoclonal, and affinity-matured gut IgA responses}},
url = {{http://dx.doi.org/10.1038/mi.2012.56}},
doi = {{10.1038/mi.2012.56}},
volume = {{6}},
year = {{2013}},
}