2026-06-14T05:17:38Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/51862024-09-27T09:26:33Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Marina-Zarate, Ester
author
Perez-Garcia, Arantxa
author
Ramiro, Almudena R
funder
Ministerio de Educación, Cultura y Deporte (España)
funder
Ministerio de Economía y Competitividad (España)
funder
Fundación ProCNIC
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
funder
Ministerio de Economía, Industria y Competitividad (España)
2017-10-20T14:56:03Z
2017-10-20T14:56:03Z
2017
Front Immunol. 2017; 8:1076
10.3389/fimmu.2017.01076
1664-3224
Frontiers in immunology
28928744
http://hdl.handle.net/20.500.12105/5186
In response to antigenic stimulation B cells undergo class switch
recombination (CSR) at the immunoglobulin heavy chain (IgH) to replace
the primary IgM/IgD isotypes by IgG, IgE, or IgA. CSR is initiated by
activation-induced cytidine deaminase (AID) through the deamination of
cytosine residues at the switch (S) regions of IgH. B cell stimulation
promotes germline transcription (GLT) of specific S regions, a necessary
event prior to CSR because it facilitates AID access to S regions. Here,
we show that CCCTC-binding factor (CTCF)-deficient mice are severely
impaired in the generation of germinal center B cells and plasma cells
after immunization in vivo, most likely due to impaired cell survival.
Importantly, we find that CTCF-deficient B cells have an increased rate
of CSR under various stimulation conditions in vitro. This effect is not
secondary to altered cell proliferation or AID expression in
CTCF-deficient cells. Instead, we find that CTCF-deficient B cells
harbor an increased mutation frequency at switch regions, probably
reflecting an increased accessibility of AID to IgH in the absence of
CTCF. Moreover, CTCF deficiency triggers premature GLT of S regions in
naive B cells. Our results indicate that CTCF restricts CSR by enforcing
GLT silencing and limiting AID access to IgH.
eng
Class switch recombination
CCCTC-binding factor
Germline transcription
Activation-induced deaminase
Somatic hypermutation
ACTIVATION-INDUCED DEAMINASE
S-MU REGION
SOMATIC HYPERMUTATION
V(D)J
RECOMBINATION
FACTOR CTCF
B-CELLS
LOCUS
ELEMENTS
AID
GENES
CCCTC-Binding Factor Locks Premature IgH Germline Transcription and
Restrains Class Switch Recombination
journal article
URL
https://repisalud.isciii.es/bitstreams/524f9313-7dec-471a-9ed3-f2ebc089718c/download
File
MD5
824a47c69d249f679e4c291b5cfed01a
3240766
application/pdf
CCCTC-BindingFactorLocks_2017
URL
https://repisalud.isciii.es/bitstreams/e434a391-7b42-4532-9d4e-4bb87f45ef20/download
File
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053e3a12ecde3bce51aa329f4058fe6c
46223
text/plain
CCCTC-BindingFactorLocks_2017.txt
URL
https://repisalud.isciii.es/bitstreams/3c4509fb-0284-49c0-8777-a6f9e0529a77/download
File
MD5
053e3a12ecde3bce51aa329f4058fe6c
46223
text/plain
CCCTC-BindingFactorLocks_2017.txt