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PTIP chromatin regulator controls development and activation of B cell subsets to license humoral immunity in mice

Su, Dan; Vanhee, Stijn LU ; Soria, Rebeca; Gyllenbäck, Elin Jaensson LU ; Starnes, Linda M.; Højfeldt, Martina Kubec; Pedersen, Gabriel K.; Yuan, Joan LU and Daniel, Jeremy A. (2017) In Proceedings of the National Academy of Sciences of the United States of America 114(44). p.9328-9337
Abstract

B cell receptor signaling and downstream NF-κB activity are crucial for the maturation and functionality of all major B cell subsets, yet the molecular players in these signaling events are not fully understood. Here we use several genetically modified mouse models to demonstrate that expression of the multifunctional BRCT (BRCA1 C-terminal) domain-containing PTIP (Pax transactivation domain-interacting protein) chromatin regulator is controlled by B cell activation and potentiates steady-state and postimmune antibody production in vivo. By examining the effects of PTIP deficiency in mice at various ages during ontogeny, we demonstrate that PTIP promotes bone marrow B cell development as well as the neonatal establishment and subsequent... (More)

B cell receptor signaling and downstream NF-κB activity are crucial for the maturation and functionality of all major B cell subsets, yet the molecular players in these signaling events are not fully understood. Here we use several genetically modified mouse models to demonstrate that expression of the multifunctional BRCT (BRCA1 C-terminal) domain-containing PTIP (Pax transactivation domain-interacting protein) chromatin regulator is controlled by B cell activation and potentiates steady-state and postimmune antibody production in vivo. By examining the effects of PTIP deficiency in mice at various ages during ontogeny, we demonstrate that PTIP promotes bone marrow B cell development as well as the neonatal establishment and subsequent long-term maintenance of self-reactive B-1 B cells. Furthermore, we find that PTIP is required for B cell receptor- and T:B interaction-induced proliferation, differentiation of follicular B cells during germinal center formation, and normal signaling through the classical NF-κB pathway. Together with the previously identified role for PTIP in promoting sterile transcription at the Igh locus, the present results establish PTIP as a licensing factor for humoral immunity that acts at several junctures of B lineage maturation and effector cell differentiation by controlling B cell activation.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Antibody, B cell biology, B-1, IgM, Immunodeficiency
in
Proceedings of the National Academy of Sciences of the United States of America
volume
114
issue
44
pages
9328 - 9337
publisher
National Acad Sciences
external identifiers
  • scopus:85032676661
  • wos:000414127400020
ISSN
0027-8424
DOI
10.1073/pnas.1707938114
language
English
LU publication?
yes
id
8a71fc73-3f1e-4c9f-83fa-0afbcf23fe37
date added to LUP
2017-11-15 07:55:04
date last changed
2018-02-15 03:00:02
@article{8a71fc73-3f1e-4c9f-83fa-0afbcf23fe37,
  abstract     = {<p>B cell receptor signaling and downstream NF-κB activity are crucial for the maturation and functionality of all major B cell subsets, yet the molecular players in these signaling events are not fully understood. Here we use several genetically modified mouse models to demonstrate that expression of the multifunctional BRCT (BRCA1 C-terminal) domain-containing PTIP (Pax transactivation domain-interacting protein) chromatin regulator is controlled by B cell activation and potentiates steady-state and postimmune antibody production in vivo. By examining the effects of PTIP deficiency in mice at various ages during ontogeny, we demonstrate that PTIP promotes bone marrow B cell development as well as the neonatal establishment and subsequent long-term maintenance of self-reactive B-1 B cells. Furthermore, we find that PTIP is required for B cell receptor- and T:B interaction-induced proliferation, differentiation of follicular B cells during germinal center formation, and normal signaling through the classical NF-κB pathway. Together with the previously identified role for PTIP in promoting sterile transcription at the Igh locus, the present results establish PTIP as a licensing factor for humoral immunity that acts at several junctures of B lineage maturation and effector cell differentiation by controlling B cell activation.</p>},
  author       = {Su, Dan and Vanhee, Stijn and Soria, Rebeca and Gyllenbäck, Elin Jaensson and Starnes, Linda M. and Højfeldt, Martina Kubec and Pedersen, Gabriel K. and Yuan, Joan and Daniel, Jeremy A.},
  issn         = {0027-8424},
  keyword      = {Antibody,B cell biology,B-1,IgM,Immunodeficiency},
  language     = {eng},
  month        = {10},
  number       = {44},
  pages        = {9328--9337},
  publisher    = {National Acad Sciences},
  series       = {Proceedings of the National Academy of Sciences of the United States of America},
  title        = {PTIP chromatin regulator controls development and activation of B cell subsets to license humoral immunity in mice},
  url          = {http://dx.doi.org/10.1073/pnas.1707938114},
  volume       = {114},
  year         = {2017},
}