Postnatal regulation of B-1a cell development and survival by the CIC-PER2-BHLHE41 axis

Hyebeen Hong; Jongeun Lee; Guk Yeol Park; Soeun Kim; Jiho Park; Jong Seok Park; Youngkwon Song; Sujin Lee; Tae Jin Kim; You Jeong Lee; Tae Young Roh; Seung Ki Kwok; Sung Won Kim; Qiumin Tan; Yoontae Lee

doi:10.1016/j.celrep.2022.110386

Postnatal regulation of B-1a cell development and survival by the CIC-PER2-BHLHE41 axis

Hyebeen Hong, Jongeun Lee, Guk Yeol Park, Soeun Kim, Jiho Park, Jong Seok Park, Youngkwon Song, Sujin Lee, Tae Jin Kim, You Jeong Lee, Tae Young Roh, Seung Ki Kwok, Sung Won Kim, Qiumin Tan, Yoontae Lee

Department of Life Science

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

Abstract

B-1 cell development mainly occurs via fetal and neonatal hematopoiesis and is suppressed in adult bone marrow hematopoiesis. However, little is known about the factors inhibiting B-1 cell development at the adult stage. We report that capicua (CIC) suppresses postnatal B-1a cell development and survival. CIC levels are high in B-1a cells and gradually increase in transitional B-1a (TrB-1a) cells with age. B-cell-specific Cic-null mice exhibit expansion of the B-1a cell population and a gradual increase in TrB-1a cell frequency with age but attenuated B-2 cell development. CIC deficiency enhances B cell receptor (BCR) signaling in transitional B cells and B-1a cell viability. Mechanistically, CIC-deficiency-mediated Per2 derepression upregulates Bhlhe41 levels by inhibiting CRY-mediated transcriptional repression for Bhlhe41, consequently promoting B-1a cell formation in Cic-null mice. Taken together, CIC is a key transcription factor that limits the B-1a cell population at the adult stage and balances B-1 versus B-2 cell formation.

Original language	English
Article number	110386
Journal	Cell Reports
Volume	38
Issue number	7
DOIs	https://doi.org/10.1016/j.celrep.2022.110386
State	Published - 15 Feb 2022

Bibliographical note

Publisher Copyright:
© 2022 The Author(s)

Keywords

B cell development
B-1a
BCR signaling
BHLHE41
PER2
TrB-1a
capicua

Access to Document

10.1016/j.celrep.2022.110386

Cite this

@article{99e41022e1574d23a32c6ed208375226,

title = "Postnatal regulation of B-1a cell development and survival by the CIC-PER2-BHLHE41 axis",

abstract = "B-1 cell development mainly occurs via fetal and neonatal hematopoiesis and is suppressed in adult bone marrow hematopoiesis. However, little is known about the factors inhibiting B-1 cell development at the adult stage. We report that capicua (CIC) suppresses postnatal B-1a cell development and survival. CIC levels are high in B-1a cells and gradually increase in transitional B-1a (TrB-1a) cells with age. B-cell-specific Cic-null mice exhibit expansion of the B-1a cell population and a gradual increase in TrB-1a cell frequency with age but attenuated B-2 cell development. CIC deficiency enhances B cell receptor (BCR) signaling in transitional B cells and B-1a cell viability. Mechanistically, CIC-deficiency-mediated Per2 derepression upregulates Bhlhe41 levels by inhibiting CRY-mediated transcriptional repression for Bhlhe41, consequently promoting B-1a cell formation in Cic-null mice. Taken together, CIC is a key transcription factor that limits the B-1a cell population at the adult stage and balances B-1 versus B-2 cell formation.",

keywords = "B cell development, B-1a, BCR signaling, BHLHE41, PER2, TrB-1a, capicua",

author = "Hyebeen Hong and Jongeun Lee and Park, {Guk Yeol} and Soeun Kim and Jiho Park and Park, {Jong Seok} and Youngkwon Song and Sujin Lee and Kim, {Tae Jin} and Lee, {You Jeong} and Roh, {Tae Young} and Kwok, {Seung Ki} and Kim, {Sung Won} and Qiumin Tan and Yoontae Lee",

note = "Publisher Copyright: {\textcopyright} 2022 The Author(s)",

year = "2022",

month = feb,

day = "15",

doi = "10.1016/j.celrep.2022.110386",

language = "English",

volume = "38",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Cell Press",

number = "7",

}

TY - JOUR

T1 - Postnatal regulation of B-1a cell development and survival by the CIC-PER2-BHLHE41 axis

AU - Hong, Hyebeen

AU - Lee, Jongeun

AU - Park, Guk Yeol

AU - Kim, Soeun

AU - Park, Jiho

AU - Park, Jong Seok

AU - Song, Youngkwon

AU - Lee, Sujin

AU - Kim, Tae Jin

AU - Lee, You Jeong

AU - Roh, Tae Young

AU - Kwok, Seung Ki

AU - Kim, Sung Won

AU - Tan, Qiumin

AU - Lee, Yoontae

PY - 2022/2/15

Y1 - 2022/2/15

N2 - B-1 cell development mainly occurs via fetal and neonatal hematopoiesis and is suppressed in adult bone marrow hematopoiesis. However, little is known about the factors inhibiting B-1 cell development at the adult stage. We report that capicua (CIC) suppresses postnatal B-1a cell development and survival. CIC levels are high in B-1a cells and gradually increase in transitional B-1a (TrB-1a) cells with age. B-cell-specific Cic-null mice exhibit expansion of the B-1a cell population and a gradual increase in TrB-1a cell frequency with age but attenuated B-2 cell development. CIC deficiency enhances B cell receptor (BCR) signaling in transitional B cells and B-1a cell viability. Mechanistically, CIC-deficiency-mediated Per2 derepression upregulates Bhlhe41 levels by inhibiting CRY-mediated transcriptional repression for Bhlhe41, consequently promoting B-1a cell formation in Cic-null mice. Taken together, CIC is a key transcription factor that limits the B-1a cell population at the adult stage and balances B-1 versus B-2 cell formation.

AB - B-1 cell development mainly occurs via fetal and neonatal hematopoiesis and is suppressed in adult bone marrow hematopoiesis. However, little is known about the factors inhibiting B-1 cell development at the adult stage. We report that capicua (CIC) suppresses postnatal B-1a cell development and survival. CIC levels are high in B-1a cells and gradually increase in transitional B-1a (TrB-1a) cells with age. B-cell-specific Cic-null mice exhibit expansion of the B-1a cell population and a gradual increase in TrB-1a cell frequency with age but attenuated B-2 cell development. CIC deficiency enhances B cell receptor (BCR) signaling in transitional B cells and B-1a cell viability. Mechanistically, CIC-deficiency-mediated Per2 derepression upregulates Bhlhe41 levels by inhibiting CRY-mediated transcriptional repression for Bhlhe41, consequently promoting B-1a cell formation in Cic-null mice. Taken together, CIC is a key transcription factor that limits the B-1a cell population at the adult stage and balances B-1 versus B-2 cell formation.

KW - B cell development

KW - B-1a

KW - BCR signaling

KW - BHLHE41

KW - PER2

KW - TrB-1a

KW - capicua

UR - http://www.scopus.com/inward/record.url?scp=85124523984&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2022.110386

DO - 10.1016/j.celrep.2022.110386

M3 - Article

C2 - 35172136

AN - SCOPUS:85124523984

SN - 2211-1247

VL - 38

JO - Cell Reports

JF - Cell Reports

IS - 7

M1 - 110386

ER -

Postnatal regulation of B-1a cell development and survival by the CIC-PER2-BHLHE41 axis

Abstract

Bibliographical note

Keywords

Access to Document

Fingerprint

Cite this