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Front. Immunol. | doi: 10.3389/fimmu.2018.00371

PTEN regulated AID transcription in germinal center B cells is essential for the class-switch recombination and IgG antibody responses

 WANLI LIU1*,  Jing Wang1 and Sichen Liu1
  • 1Tsinghua University, China

Class-switch recombination (CSR) and somatic hypermutation (SHM) occur during the differentiation of germinal center B cells (GCBs). Activation-induced cytidine deaminase (AID) is responsible for both CSR and SHM in GCBs. Here we show that ablation of PTEN through the Cγ1-Cre mediated recombination significantly influences the CSR and SHM responses. The GCs fail to produce the IgG1 B cells, the high affinity antibodies and nearly lost the dark zone (DZ) in Ptenfl/fl Cγ1Cre/+ mice after immunization, suggesting the impaired GC structure. Further mechanistic investigations show that LPS- and IL-4 stimulation induced the transcription of Cγ1 in IgM-BCR expressing B cells, which efficiently disrupts PTEN transcription, results in the hyper-phosphorylated AKT and FoxO1 and in turn the suppression of AID transcription. Additionally, the reduced transcription of PTEN and AID are also validated by investigating the IgM-BCR expressing GCBs from Ptenfl/fl Cγ1Cre/+ mice upon immunization. In conclusion, PTEN regulated AID transcription in germinal center B cells is essential for the class-switch recombination and IgG antibody responses.

Keywords: Pten, Germinal Center, IgG1 B cells, CSR, SHM

Received: 04 Aug 2017; Accepted: 09 Feb 2018.

Edited by:

Raffi Gugasyan, Burnet Institute, Australia

Reviewed by:

Wenxia Song, University of Maryland, College Park, United States
Kang Chen, Wayne State University, United States  

Copyright: © 2018 LIU, Wang and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: PhD. WANLI LIU, Tsinghua University, Beijing, China, LIUWANLI@BIOMED.TSINGHUA.EDU.CN