| Autor: |
Delgado-Benito, Verónica, Berruezo-Llacuna, Maria, Altwasser, Robert, Winkler, Wiebke, Sundaravinayagam, Devakumar, Balasubramanian, Sandhya, Caganova, Marieta, Graf, Robin, Rahjouei, Ali, Henke, Marie-Thérèse, Driesner, Madlen, Keller, Lisa, Prigione, Alessandro, Janz, Martin, Akalin, Altuna, Di Virgilio, Michela |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
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| Popis: |
The establishment of protective humoral immunity is dependent on the ability of mature B cells to undergo antibody gene diversification while adjusting to the physiological stressors induced by activation with the antigen. Mature B cells diversify their antibody genes by class switch recombination (CSR) and somatic hypermutation (SHM), which are both dependent on efficient induction of activation-induced cytidine deaminase (AID). Here, we identified PDGFA-associated protein 1 (Pdap1) as an essential regulator of cellular homeostasis in mature B cells. Pdap1 deficiency leads to sustained expression of the integrated stress response (ISR) effector activating transcription factor 4 (Atf4) and induction of the ISR transcriptional program, increased cell death, and defective AID expression. As a consequence, loss of Pdap1 reduces germinal center B cell formation and impairs CSR and SHM. Thus, Pdap1 protects mature B cells against chronic ISR activation and ensures efficient antibody diversification by promoting their survival and optimal function. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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