PMID- 34260907
OWN - NLM
STAT- MEDLINE
DCOM- 20220208
LR  - 20240402
IS  - 2211-1247 (Electronic)
VI  - 36
IP  - 2
DP  - 2021 Jul 13
TI  - IL-7R signaling activates widespread V(H) and D(H) gene usage to drive antibody 
      diversity in bone marrow B cells.
PG  - 109349
LID - S2211-1247(21)00725-7 [pii]
LID - 10.1016/j.celrep.2021.109349 [doi]
LID - 109349
AB  - Generation of the primary antibody repertoire requires V(D)J recombination of 
      hundreds of gene segments in the immunoglobulin heavy chain (Igh) locus. The role 
      of interleukin-7 receptor (IL-7R) signaling in Igh recombination has been 
      difficult to partition from its role in B cell survival and proliferation. With a 
      detailed description of the Igh repertoire in murine IL-7Ralpha(-/-) bone marrow B 
      cells, we demonstrate that IL-7R signaling profoundly influences V(H) gene 
      selection during V(H)-to-DJ(H) recombination. We find skewing toward 3' V(H) 
      genes during de novo V(H)-to-DJ(H) recombination more severe than the fetal liver 
      (FL) repertoire and uncover a role for IL-7R signaling in D(H)-to-J(H) 
      recombination. Transcriptome and accessibility analyses suggest reduced 
      expression of B lineage transcription factors (TFs) and targets and loss of D(H) 
      and V(H) antisense transcription in IL-7Ralpha(-/-) B cells. Thus, in addition to its 
      roles in survival and proliferation, IL-7R signaling shapes the Igh repertoire by 
      activating underpinning mechanisms.
CI  - Copyright (c) 2021 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Baizan-Edge, Amanda
AU  - Baizan-Edge A
AD  - Nuclear Dynamics Programme, Babraham Institute, Babraham Research Campus, 
      Cambridge CB22 3AT, UK.
FAU - Stubbs, Bryony A
AU  - Stubbs BA
AD  - Nuclear Dynamics Programme, Babraham Institute, Babraham Research Campus, 
      Cambridge CB22 3AT, UK.
FAU - Stubbington, Michael J T
AU  - Stubbington MJT
AD  - Nuclear Dynamics Programme, Babraham Institute, Babraham Research Campus, 
      Cambridge CB22 3AT, UK.
FAU - Bolland, Daniel J
AU  - Bolland DJ
AD  - Nuclear Dynamics Programme, Babraham Institute, Babraham Research Campus, 
      Cambridge CB22 3AT, UK; Lymphocyte Signaling and Development Programme, Babraham 
      Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
FAU - Tabbada, Kristina
AU  - Tabbada K
AD  - Nuclear Dynamics Programme, Babraham Institute, Babraham Research Campus, 
      Cambridge CB22 3AT, UK; Lymphocyte Signaling and Development Programme, Babraham 
      Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
FAU - Andrews, Simon
AU  - Andrews S
AD  - Bioinformatics Group, Babraham Institute, Babraham Research Campus, Cambridge 
      CB22 3AT, UK.
FAU - Corcoran, Anne E
AU  - Corcoran AE
AD  - Nuclear Dynamics Programme, Babraham Institute, Babraham Research Campus, 
      Cambridge CB22 3AT, UK; Lymphocyte Signaling and Development Programme, Babraham 
      Institute, Babraham Research Campus, Cambridge CB22 3AT, UK. Electronic address: 
      anne.corcoran@babraham.ac.uk.
LA  - eng
GR  - BBS/E/B/000C0404/BB_/Biotechnology and Biological Sciences Research 
      Council/United Kingdom
GR  - BBS/E/B/000C0405/BB_/Biotechnology and Biological Sciences Research 
      Council/United Kingdom
GR  - BBS/E/B/000C0427/BB_/Biotechnology and Biological Sciences Research 
      Council/United Kingdom
GR  - BBS/E/B/000C0428/BB_/Biotechnology and Biological Sciences Research 
      Council/United Kingdom
GR  - 1236141/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell Rep
JT  - Cell reports
JID - 101573691
RN  - 0 (Chromatin)
RN  - 0 (DNA, Intergenic)
RN  - 0 (Ebf1 protein, mouse)
RN  - 0 (Immunoglobulin Variable Region)
RN  - 0 (PAX5 Transcription Factor)
RN  - 0 (Receptors, Interleukin-7)
RN  - 0 (Trans-Activators)
SB  - IM
MH  - Animals
MH  - Antibody Diversity/*genetics
MH  - B-Lymphocytes/*metabolism
MH  - Base Sequence
MH  - Bone Marrow/*metabolism
MH  - Cell Lineage/genetics
MH  - Chromatin/metabolism
MH  - DNA, Intergenic/genetics
MH  - Fetus/metabolism
MH  - *Genes, Immunoglobulin Heavy Chain
MH  - Immunoglobulin Variable Region/*genetics
MH  - Liver/embryology/metabolism
MH  - Mice, Inbred C57BL
MH  - Nucleotide Motifs/genetics
MH  - PAX5 Transcription Factor/metabolism
MH  - Receptors, Interleukin-7/*metabolism
MH  - *Signal Transduction
MH  - Trans-Activators/metabolism
MH  - Transcription, Genetic
MH  - Mice
PMC - PMC8293627
OTO - NOTNLM
OT  - B lymphocyte development
OT  - Igh recombination
OT  - Pax5 transcription factor
OT  - antisense transcription
OT  - bone marrow
OT  - chromatin accessibility
OT  - fetal liver
OT  - interleukin-7 receptor signaling
OT  - pro-B cells
COIS- Declaration of interests D.J.B. and A.E.C. are inventors on a patent method of 
      identifying VDJ recombination products, published in 2013, PCT/GB2O13/050516 and 
      WO2013128204A1; in 2015, US2015/0031042; and in 2017, US9797014B2. M.J.T.S. is an 
      employee and share- and option-holder of 10x Genomics.
EDAT- 2021/07/15 06:00
MHDA- 2022/02/09 06:00
PMCR- 2021/07/13
CRDT- 2021/07/14 20:06
PHST- 2020/12/09 00:00 [received]
PHST- 2021/04/05 00:00 [revised]
PHST- 2021/06/15 00:00 [accepted]
PHST- 2021/07/14 20:06 [entrez]
PHST- 2021/07/15 06:00 [pubmed]
PHST- 2022/02/09 06:00 [medline]
PHST- 2021/07/13 00:00 [pmc-release]
AID - S2211-1247(21)00725-7 [pii]
AID - 109349 [pii]
AID - 10.1016/j.celrep.2021.109349 [doi]
PST - ppublish
SO  - Cell Rep. 2021 Jul 13;36(2):109349. doi: 10.1016/j.celrep.2021.109349.