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.

转录因子 Pax5 控制 B 细胞发育，但它在成熟 B 细胞中的作用在很大程度上是神秘的。在这里，我们证明了外周 B 淋巴细胞中条件诱变导致 Pax5 的丢失导致 B-1a、边缘区 (MZ) 和生发中心 (GC) B 细胞以及浆细胞的强烈减少。滤泡 (FO) B 细胞耐受 Pax5 的丢失，但半衰期缩短。由于 PI3K-AKT 信号传导受损，Pax5 缺陷型 FO B 细胞未能在 B 细胞受体或 Toll 样受体刺激下增殖，这是由 PTEN（PI3K 通路的负调节因子）的表达增加引起的。Pax5 在转录后水平抑制 PTEN 蛋白表达，可能涉及Pten靶向 microRNA。Pten,Pax5中的额外 PTEN 损失双突变小鼠挽救了 FO B 细胞数量和 MZ B 细胞的发育，但没有恢复 GC B 细胞的形成。因此，PTEN表达的转录后下调是Pax5的一个重要功能，它促进成熟B细胞的分化和存活，从而促进体液免疫。