Abstract
Ig class switching requires cell proliferation and is division linked, but the detailed mechanism is unknown. By analyzing the first switching cells early in the kinetics, our analysis suggested that proliferating B cells had a very short G1 phase (<3.5 h), a total cell cycle time of ∼11 h, and that Ig class switching preferentially occurred in the late G 1 or early S phase. Inhibition of cyclin-dependent kinases (CDKs) caused dramatic reduction of switching rate within 6 h. This was associated with less targeting of activation-induced cytidine deaminase (AID) to the Igh locus. Interestingly, ectopically expressed nuclear AID in HeLa cells was preferentially found in the early S phase. Furthermore, in CDK2 hypomorphic cells there was reduced nuclear AID accumulation. Thus, our data are compatible with the idea that division-linked Ig class switching is in part due to CDK2-regulated AID nuclear access at the G<inf>1</inf>/S border.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 4231-4239 |
| Number of pages | 9 |
| Journal | Journal of Immunology |
| Volume | 194 |
| Issue number | 9 |
| DOIs | |
| State | Published - May 1 2015 |
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ASJC Scopus subject areas
- Immunology
Cite this
Cyclin-dependent kinases regulate Ig class switching by controlling access of AID to the switch region. / He, Minghui; Cortizas, Elena M.; Verdun, Ramiro E; Severinson, Eva.
In: Journal of Immunology, Vol. 194, No. 9, 01.05.2015, p. 4231-4239.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Cyclin-dependent kinases regulate Ig class switching by controlling access of AID to the switch region
AU - He, Minghui
AU - Cortizas, Elena M.
AU - Verdun, Ramiro E
AU - Severinson, Eva
PY - 2015/5/1
Y1 - 2015/5/1
N2 - Ig class switching requires cell proliferation and is division linked, but the detailed mechanism is unknown. By analyzing the first switching cells early in the kinetics, our analysis suggested that proliferating B cells had a very short G1 phase (<3.5 h), a total cell cycle time of ∼11 h, and that Ig class switching preferentially occurred in the late G 1 or early S phase. Inhibition of cyclin-dependent kinases (CDKs) caused dramatic reduction of switching rate within 6 h. This was associated with less targeting of activation-induced cytidine deaminase (AID) to the Igh locus. Interestingly, ectopically expressed nuclear AID in HeLa cells was preferentially found in the early S phase. Furthermore, in CDK2 hypomorphic cells there was reduced nuclear AID accumulation. Thus, our data are compatible with the idea that division-linked Ig class switching is in part due to CDK2-regulated AID nuclear access at the G1/S border.
AB - Ig class switching requires cell proliferation and is division linked, but the detailed mechanism is unknown. By analyzing the first switching cells early in the kinetics, our analysis suggested that proliferating B cells had a very short G1 phase (<3.5 h), a total cell cycle time of ∼11 h, and that Ig class switching preferentially occurred in the late G 1 or early S phase. Inhibition of cyclin-dependent kinases (CDKs) caused dramatic reduction of switching rate within 6 h. This was associated with less targeting of activation-induced cytidine deaminase (AID) to the Igh locus. Interestingly, ectopically expressed nuclear AID in HeLa cells was preferentially found in the early S phase. Furthermore, in CDK2 hypomorphic cells there was reduced nuclear AID accumulation. Thus, our data are compatible with the idea that division-linked Ig class switching is in part due to CDK2-regulated AID nuclear access at the G1/S border.
UR - http://www.scopus.com/inward/record.url?scp=84928501046&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84928501046&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1402146
DO - 10.4049/jimmunol.1402146
M3 - Article
VL - 194
SP - 4231
EP - 4239
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 9
ER -