Pax5 regulates B cell immunity by promoting PI3K signaling via PTEN down-regulation

Lesly Calderón, Karina Schindler, Stephen G. Malin, Alexandra Schebesta, Qiong Sun, Tanja Schwickert, Chiara Alberti, Maria Fischer, Markus Jaritz, Hiromi Tagoh, Anja Ebert, Martina Minnich, Adrian Liston, Luisa Cochella, Meinrad Busslinger

Research output: Contribution to journalArticlepeer-review


The transcription factor Pax5 controls B cell development, but its role in mature B cells is largely enigmatic. Here, we demonstrated that the loss of Pax5 by conditional mutagenesis in peripheral B lymphocytes led to the strong reduction of B-1a, marginal zone (MZ), and germinal center (GC) B cells as well as plasma cells. Follicular (FO) B cells tolerated the loss of Pax5 but had a shortened half-life. The Pax5-deficient FO B cells failed to proliferate upon B cell receptor or Toll-like receptor stimulation due to impaired PI3K-AKT signaling, which was caused by increased expression of PTEN, a negative regulator of the PI3K pathway. Pax5 restrained PTEN protein expression at the posttranscriptional level, likely involving Pten-targeting microRNAs. Additional PTEN loss in Pten,Pax5 double-mutant mice rescued FO B cell numbers and the development of MZ B cells but did not restore GC B cell formation. Hence, the posttranscriptional down-regulation of PTEN expression is an important function of Pax5 that facilitates the differentiation and survival of mature B cells, thereby promoting humoral immunity.

Original languageEnglish (US)
Article numbereabg5003
JournalScience Immunology
Issue number61
StatePublished - Jul 2021
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


Dive into the research topics of 'Pax5 regulates B cell immunity by promoting PI3K signaling via PTEN down-regulation'. Together they form a unique fingerprint.

Cite this