Oxygen level is a critical regulator of human B cell differentiation and IgG class switch recombination

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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 in pO2 affect B cell differentiation, in particular for humans. Using optimized in vitro cultures 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 normoxic pO2 during culture - reminiscent of in vivo GC 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.
Original languageEnglish
Article number1082154
Number of pages15
JournalFrontiers in immunology
Publication statusPublished - 14 Dec 2022


  • B cells
  • B-Lymphocytes
  • Cell Differentiation
  • Humans
  • Hypoxia/metabolism
  • Immunoglobulin G
  • Oxygen/metabolism
  • antibody-secreting cell
  • class switch recombination
  • differentiation
  • germinal center
  • hypoxia

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