TY - JOUR TI - Pax5 regulates B cell immunity by promoting PI3K signaling via PTEN down-regulation AU - Calderón, Lesly AU - Schindler, Karina AU - Malin, Stephen G. AU - Schebesta, Alexandra AU - Sun, Qiong AU - Schwickert, Tanja AU - Alberti, Chiara AU - Fischer, Maria AU - Jaritz, Markus AU - Tagoh, Hiromi AU - Ebert, Anja AU - Minnich, Martina AU - Liston, Adrian AU - Cochella, Luisa AU - Busslinger, Meinrad T2 - Science Immunology AB - Pax5 regulates mature B cell B cells are a crucial part of adaptive immune responses, so better understanding their development and maturation is crucial. B cell development is controlled by the transcription factor Pax5, but it is not known whether Pax5 regulates B cell maturation. To study how Pax5 affected B cell maturation, Calderón et al. created a mouse model with a specific deletion of Pax5 in immature B cells. They found that these mice had reduced B-1a, marginal zone, germinal center B cells, and plasma cells, as well as decreased survival and proliferation of follicular B cells. These defects were due to impaired PI3K-AKT signaling via increased PTEN expression in the Pax5-deficient B cells. Thus, Pax5 regulates both the development and maturation of B cells. 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. Pax5 controls the generation, proliferation, and survival of all mature B cells by promoting PI3K signaling via PTEN down-regulation. Pax5 controls the generation, proliferation, and survival of all mature B cells by promoting PI3K signaling via PTEN down-regulation. DA - 2021/07/23/ PY - 2021 DO - 10.1126/sciimmunol.abg5003 DP - immunology.sciencemag.org VL - 6 IS - 61 LA - en SN - 2470-9468 UR - https://immunology.sciencemag.org/content/6/61/eabg5003 Y2 - 2021/07/27/16:59:02 ER -