T cell-independent IgA class switch recombination is restricted to the GALT and occurs prior to manifest germinal center formation
Bergqvist, Peter ; Stensson, Anneli ; Lycke, Nils Y. and Bemark, Mats LU
(2010)
In Journal of Immunology
184(7).
p.3545-3553
- Abstract
Recently, we reported that CD40-/- mice, exhibiting exclusively T cell-independent IgA class switch recombination (CSR), demonstrated near normal levels of IgA plasma cells in the gut lamina propria (LP), despite the complete lack of germinal centers (GCs). In this study, we have extended our analysis focusing on how to reconcile these findings using flow cytometry and molecular markers for IgA CSR. In agreement with our previous results with small intestinal LP, the colon LP was found to host IgA CSR only when lymphoid follicles were present. Thus, no IgA CSR was observed in the nonorganized colon LP. By contrast, the Peyer's patch (PP) was the dominant IgA CSR site in both CD40-/- and wild type (WT) mice, and... (More)
Recently, we reported that CD40-/- mice, exhibiting exclusively T cell-independent IgA class switch recombination (CSR), demonstrated near normal levels of IgA plasma cells in the gut lamina propria (LP), despite the complete lack of germinal centers (GCs). In this study, we have extended our analysis focusing on how to reconcile these findings using flow cytometry and molecular markers for IgA CSR. In agreement with our previous results with small intestinal LP, the colon LP was found to host IgA CSR only when lymphoid follicles were present. Thus, no IgA CSR was observed in the nonorganized colon LP. By contrast, the Peyer's patch (PP) was the dominant IgA CSR site in both CD40-/- and wild type (WT) mice, and they both hosted similar levels of mRNA expression for B cell activating factor of the TNF family, a proliferation inducing ligand, and inducible NO synthase, potential switch-factors for IgA. Unexpectedly, we found that PP B cells undergoing IgA CSR were GL7-intermediate. These cells had not undergone somatic hypermutations (SHMs), whereas GL7-high cells in WT PP, which exhibited GCs, were heavily mutated. Moreover, IgA plasma cells in the LP of CD40-/- mice demonstrated few mutations in their Ig V regions, whereas WT LP B cells from different sites showed extensive SHMs, which were also clonally related. Therefore, IgA CSR can occur in PP at a stage preceding manifest GC (GL7-intermediate), whereas SHM require GC formations (GL7-high). These findings reconcile that IgA CSR can occur in PP in the absence of GC with the fact that CD40-/- mice host near normal levels of IgA plasma cells in the LP.
(Less)
- author
- Bergqvist, Peter
; Stensson, Anneli
; Lycke, Nils Y.
and Bemark, Mats
LU
- publishing date
- 2010-04-01
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Immunology
- volume
- 184
- issue
- 7
- pages
- 3545 - 3553
- publisher
- American Association of Immunologists
- external identifiers
-
- pmid:20207993
- scopus:77951639699
- ISSN
- 0022-1767
- DOI
- 10.4049/jimmunol.0901895
- language
- English
- LU publication?
- no
- id
- 50302df1-1f18-470b-96c6-cdeb525d0b9d
- date added to LUP
- 2023-12-06 17:01:13
- date last changed
- 2024-04-05 07:42:03
@article{50302df1-1f18-470b-96c6-cdeb525d0b9d,
abstract = {{<p>Recently, we reported that CD40<sup>-/-</sup> mice, exhibiting exclusively T cell-independent IgA class switch recombination (CSR), demonstrated near normal levels of IgA plasma cells in the gut lamina propria (LP), despite the complete lack of germinal centers (GCs). In this study, we have extended our analysis focusing on how to reconcile these findings using flow cytometry and molecular markers for IgA CSR. In agreement with our previous results with small intestinal LP, the colon LP was found to host IgA CSR only when lymphoid follicles were present. Thus, no IgA CSR was observed in the nonorganized colon LP. By contrast, the Peyer's patch (PP) was the dominant IgA CSR site in both CD40<sup>-/-</sup> and wild type (WT) mice, and they both hosted similar levels of mRNA expression for B cell activating factor of the TNF family, a proliferation inducing ligand, and inducible NO synthase, potential switch-factors for IgA. Unexpectedly, we found that PP B cells undergoing IgA CSR were GL7-intermediate. These cells had not undergone somatic hypermutations (SHMs), whereas GL7-high cells in WT PP, which exhibited GCs, were heavily mutated. Moreover, IgA plasma cells in the LP of CD40<sup>-/-</sup> mice demonstrated few mutations in their Ig V regions, whereas WT LP B cells from different sites showed extensive SHMs, which were also clonally related. Therefore, IgA CSR can occur in PP at a stage preceding manifest GC (GL7-intermediate), whereas SHM require GC formations (GL7-high). These findings reconcile that IgA CSR can occur in PP in the absence of GC with the fact that CD40<sup>-/-</sup> mice host near normal levels of IgA plasma cells in the LP.</p>}},
author = {{Bergqvist, Peter and Stensson, Anneli and Lycke, Nils Y. and Bemark, Mats}},
issn = {{0022-1767}},
language = {{eng}},
month = {{04}},
number = {{7}},
pages = {{3545--3553}},
publisher = {{American Association of Immunologists}},
series = {{Journal of Immunology}},
title = {{T cell-independent IgA class switch recombination is restricted to the GALT and occurs prior to manifest germinal center formation}},
url = {{http://dx.doi.org/10.4049/jimmunol.0901895}},
doi = {{10.4049/jimmunol.0901895}},
volume = {{184}},
year = {{2010}},
}