Murine germinal center B cells require functional fms-like tyrosine kinase 3 signaling for IgG1 class-switch recombination
Svensson, Mattias N.D. ; Andersson, Karin M.E. ; Wasén, Caroline ; Erlandsson, Malin C. ; Nurkkala-Karlsson, Merja ; Jonsson, Ing Marie ; Brisslert, Mikael ; Bemark, Mats LU
and Bokarewa, Maria I.
(2015)
In Proceedings of the National Academy of Sciences of the United States of America
112(48).
p.6644-6653
- Abstract
Switched antibody classes are important for efficient immune responses. Aberrant antibody production to otherwise harmless antigens may result in autoimmunity. The protein kinase fms-like tyrosine kinase 3 receptor (Flt3) has an important role during early B-cell development, but the role of Flt3 in peripheral B cells has not been assessed before. Herein we describe a previously unappreciated role for Flt3 in IgG1 class-switch recombination (CSR) and production. We show that Flt3 is reexpressed on B-cell lymphoma 6+ germinal center B cells in vivo and following LPS activation of peripheral B cells in vitro. Absence of Flt3 signaling in Flt3 liganddeficient mice results in impaired IgG1 CSR and accumulation of IgM-secreting plasma cells.... (More)
Switched antibody classes are important for efficient immune responses. Aberrant antibody production to otherwise harmless antigens may result in autoimmunity. The protein kinase fms-like tyrosine kinase 3 receptor (Flt3) has an important role during early B-cell development, but the role of Flt3 in peripheral B cells has not been assessed before. Herein we describe a previously unappreciated role for Flt3 in IgG1 class-switch recombination (CSR) and production. We show that Flt3 is reexpressed on B-cell lymphoma 6+ germinal center B cells in vivo and following LPS activation of peripheral B cells in vitro. Absence of Flt3 signaling in Flt3 liganddeficient mice results in impaired IgG1 CSR and accumulation of IgM-secreting plasma cells. On activated B cells, Flt3 is coexpressed and functions in synergy with the common-gamma chain receptor family. B cells from Flt3 ligand-deficient mice have impaired IL-4R signaling, with reduced phosphorylation of signal transducer and activator of transcription (Stat) 6, and demonstrate a failure to initiate CSR to IgG1 with low expression of γ1 germ-line transcripts, resulting in impaired IgG1 production. Thus, functional synergy between Flt3 and IL-4R signaling is critical for Stat-mediated regulation of sterile γ1 germ-line transcripts and CSR to IgG1.
(Less)
- author
- Svensson, Mattias N.D.
; Andersson, Karin M.E.
; Wasén, Caroline
; Erlandsson, Malin C.
; Nurkkala-Karlsson, Merja
; Jonsson, Ing Marie
; Brisslert, Mikael
; Bemark, Mats
LU
and Bokarewa, Maria I.
- publishing date
- 2015-12-01
- type
- Contribution to journal
- publication status
- published
- keywords
- Class-switch recombination, Flt3, Germinal center B cells, IgG1, IL-4R
- in
- Proceedings of the National Academy of Sciences of the United States of America
- volume
- 112
- issue
- 48
- pages
- 6644 - 6653
- publisher
- National Academy of Sciences
- external identifiers
-
- pmid:26627255
- scopus:84948655231
- ISSN
- 0027-8424
- DOI
- 10.1073/pnas.1514191112
- language
- English
- LU publication?
- no
- id
- d0716fde-116a-487b-b95a-2fdc4cddbfa0
- date added to LUP
- 2023-12-06 16:57:11
- date last changed
- 2024-01-04 15:20:14
@article{d0716fde-116a-487b-b95a-2fdc4cddbfa0,
abstract = {{<p>Switched antibody classes are important for efficient immune responses. Aberrant antibody production to otherwise harmless antigens may result in autoimmunity. The protein kinase fms-like tyrosine kinase 3 receptor (Flt3) has an important role during early B-cell development, but the role of Flt3 in peripheral B cells has not been assessed before. Herein we describe a previously unappreciated role for Flt3 in IgG1 class-switch recombination (CSR) and production. We show that Flt3 is reexpressed on B-cell lymphoma 6+ germinal center B cells in vivo and following LPS activation of peripheral B cells in vitro. Absence of Flt3 signaling in Flt3 liganddeficient mice results in impaired IgG1 CSR and accumulation of IgM-secreting plasma cells. On activated B cells, Flt3 is coexpressed and functions in synergy with the common-gamma chain receptor family. B cells from Flt3 ligand-deficient mice have impaired IL-4R signaling, with reduced phosphorylation of signal transducer and activator of transcription (Stat) 6, and demonstrate a failure to initiate CSR to IgG1 with low expression of γ1 germ-line transcripts, resulting in impaired IgG1 production. Thus, functional synergy between Flt3 and IL-4R signaling is critical for Stat-mediated regulation of sterile γ1 germ-line transcripts and CSR to IgG1.</p>}},
author = {{Svensson, Mattias N.D. and Andersson, Karin M.E. and Wasén, Caroline and Erlandsson, Malin C. and Nurkkala-Karlsson, Merja and Jonsson, Ing Marie and Brisslert, Mikael and Bemark, Mats and Bokarewa, Maria I.}},
issn = {{0027-8424}},
keywords = {{Class-switch recombination; Flt3; Germinal center B cells; IgG1; IL-4R}},
language = {{eng}},
month = {{12}},
number = {{48}},
pages = {{6644--6653}},
publisher = {{National Academy of Sciences}},
series = {{Proceedings of the National Academy of Sciences of the United States of America}},
title = {{Murine germinal center B cells require functional fms-like tyrosine kinase 3 signaling for IgG1 class-switch recombination}},
url = {{http://dx.doi.org/10.1073/pnas.1514191112}},
doi = {{10.1073/pnas.1514191112}},
volume = {{112}},
year = {{2015}},
}