Oxygen level is a critical regulator of human B cell differentiation and IgG class switch recombination
| Autor: | Koers, J., Marsman, C., Steuten, J., Tol, S., Derksen, N.I.L., ten Brinke, A., van Ham, S., Rispens, T. |
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| Přispěvatelé: | Graduate School, AII - Inflammatory diseases, Landsteiner Laboratory, SILS Other Research (FNWI) |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Frontiers in immunology, 13:1082154. Frontiers Media S.A. Frontiers in Immunology, 13:1082154. Frontiers Media S.A. |
| ISSN: | 1664-3224 |
| Popis: | The generation of high-affinity antibodies requires an efficient germinal center (GC) response. As differentiating B cells cycle between GC dark and light zones they encounter different oxygen pressures (pO2). However, it is essentially unknown if and how variations inpO2affect B cell differentiation, in particular for humans. Using optimizedin vitrocultures together with in-depth assessment of B cell phenotype and signaling pathways, we show that oxygen is a critical regulator of human naive B cell differentiation and class switch recombination. Normoxia promotes differentiation into functional antibody secreting cells, while a population of CD27++B cells was uniquely generated under hypoxia. Moreover, time-dependent transitions between hypoxic and normoxicpO2during culture - reminiscent ofin vivoGC cyclic re-entry - steer different human B cell differentiation trajectories and IgG class switch recombination. Taken together, we identified multiple mechanisms trough which oxygen pressure governs human B cell differentiation. |
| Databáze: | OpenAIRE |
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