BCR affinity differentially regulates colonization of the subepithelial dome and infiltration into germinal centers within Peyer’s patches
Biram, Adi ; Strömberg, Anneli ; Winter, Eitan ; Stoler-Barak, Liat ; Salomon, Ran ; Addadi, Yoseph ; Dahan, Rony ; Yaari, Gur ; Bemark, Mats LU
and Shulman, Ziv
(2019)
In Nature Immunology
20(4).
p.482-492
- Abstract
Gut-derived antigens trigger immunoglobulin A (IgA) immune responses that are initiated by cognate B cells in Peyer’s patches (PPs). These cells colonize the subepithelial domes (SEDs) of the PPs and subsequently infiltrate pre-existing germinal centers (GCs). Here we defined the pre-GC events and the micro-anatomical site at which affinity-based B cell selection occurred in PPs. Using whole-organ imaging, we showed that the affinity of the B cell antigen receptor (BCR) regulated the infiltration of antigen-specific B cells into GCs but not clonal competition in the SED. Follicular helper-like T cells resided in the SED and promoted its B cell colonization, independently of the magnitude of BCR affinity. Imaging and immunoglobulin... (More)
Gut-derived antigens trigger immunoglobulin A (IgA) immune responses that are initiated by cognate B cells in Peyer’s patches (PPs). These cells colonize the subepithelial domes (SEDs) of the PPs and subsequently infiltrate pre-existing germinal centers (GCs). Here we defined the pre-GC events and the micro-anatomical site at which affinity-based B cell selection occurred in PPs. Using whole-organ imaging, we showed that the affinity of the B cell antigen receptor (BCR) regulated the infiltration of antigen-specific B cells into GCs but not clonal competition in the SED. Follicular helper-like T cells resided in the SED and promoted its B cell colonization, independently of the magnitude of BCR affinity. Imaging and immunoglobulin sequencing indicated that selective clonal expansion ensued during infiltration into GCs. Thus, in contrast to the events in draining lymph nodes and spleen, in PPs, T cells promoted mainly the population expansion of B cells without clonal selection during pre-GC events. These findings have major implications for the design of oral vaccines.
(Less)
- author
- Biram, Adi
; Strömberg, Anneli
; Winter, Eitan
; Stoler-Barak, Liat
; Salomon, Ran
; Addadi, Yoseph
; Dahan, Rony
; Yaari, Gur
; Bemark, Mats
LU
and Shulman, Ziv
- publishing date
- 2019-04-01
- type
- Contribution to journal
- publication status
- published
- in
- Nature Immunology
- volume
- 20
- issue
- 4
- pages
- 482 - 492
- publisher
- Nature Publishing Group
- external identifiers
-
- pmid:30833793
- scopus:85062439563
- ISSN
- 1529-2908
- DOI
- 10.1038/s41590-019-0325-1
- language
- English
- LU publication?
- no
- additional info
- Publisher Copyright: © 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.
- id
- 76dfcdcf-d9b5-4466-b729-2a481f55157b
- date added to LUP
- 2023-12-06 17:02:40
- date last changed
- 2024-04-05 09:17:00
@article{76dfcdcf-d9b5-4466-b729-2a481f55157b,
abstract = {{<p>Gut-derived antigens trigger immunoglobulin A (IgA) immune responses that are initiated by cognate B cells in Peyer’s patches (PPs). These cells colonize the subepithelial domes (SEDs) of the PPs and subsequently infiltrate pre-existing germinal centers (GCs). Here we defined the pre-GC events and the micro-anatomical site at which affinity-based B cell selection occurred in PPs. Using whole-organ imaging, we showed that the affinity of the B cell antigen receptor (BCR) regulated the infiltration of antigen-specific B cells into GCs but not clonal competition in the SED. Follicular helper-like T cells resided in the SED and promoted its B cell colonization, independently of the magnitude of BCR affinity. Imaging and immunoglobulin sequencing indicated that selective clonal expansion ensued during infiltration into GCs. Thus, in contrast to the events in draining lymph nodes and spleen, in PPs, T cells promoted mainly the population expansion of B cells without clonal selection during pre-GC events. These findings have major implications for the design of oral vaccines.</p>}},
author = {{Biram, Adi and Strömberg, Anneli and Winter, Eitan and Stoler-Barak, Liat and Salomon, Ran and Addadi, Yoseph and Dahan, Rony and Yaari, Gur and Bemark, Mats and Shulman, Ziv}},
issn = {{1529-2908}},
language = {{eng}},
month = {{04}},
number = {{4}},
pages = {{482--492}},
publisher = {{Nature Publishing Group}},
series = {{Nature Immunology}},
title = {{BCR affinity differentially regulates colonization of the subepithelial dome and infiltration into germinal centers within Peyer’s patches}},
url = {{http://dx.doi.org/10.1038/s41590-019-0325-1}},
doi = {{10.1038/s41590-019-0325-1}},
volume = {{20}},
year = {{2019}},
}