Oxygen level is a critical regulator of human B cell differentiation and IgG class switch recombination
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 differentiat...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-12-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1082154/full |
| _version_ | 1811200165734776832 |
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| author | Jana Koers Casper Marsman Juulke Steuten Simon Tol Ninotska I. L. Derksen Anja ten Brinke S. Marieke van Ham S. Marieke van Ham Theo Rispens |
| author_facet | Jana Koers Casper Marsman Juulke Steuten Simon Tol Ninotska I. L. Derksen Anja ten Brinke S. Marieke van Ham S. Marieke van Ham Theo Rispens |
| author_sort | Jana Koers |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T02:00:15Z |
| format | Article |
| id | doaj.art-5c4701492b4443feb08d74297f0074cc |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T02:00:15Z |
| publishDate | 2022-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-5c4701492b4443feb08d74297f0074cc2022-12-22T03:52:41ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-12-011310.3389/fimmu.2022.10821541082154Oxygen level is a critical regulator of human B cell differentiation and IgG class switch recombinationJana Koers0Casper Marsman1Juulke Steuten2Simon Tol3Ninotska I. L. Derksen4Anja ten Brinke5S. Marieke van Ham6S. Marieke van Ham7Theo Rispens8Department of Immunopathology, and Landsteiner Laboratory, Sanquin Research, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, NetherlandsDepartment of Immunopathology, and Landsteiner Laboratory, Sanquin Research, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, NetherlandsDepartment of Immunopathology, and Landsteiner Laboratory, Sanquin Research, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, NetherlandsDepartment of Research Facilities, and Landsteiner Laboratory, Sanquin Research, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, NetherlandsDepartment of Immunopathology, and Landsteiner Laboratory, Sanquin Research, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, NetherlandsDepartment of Immunopathology, and Landsteiner Laboratory, Sanquin Research, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, NetherlandsDepartment of Immunopathology, and Landsteiner Laboratory, Sanquin Research, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, NetherlandsSwammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, NetherlandsDepartment of Immunopathology, and Landsteiner Laboratory, Sanquin Research, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, NetherlandsThe 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.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1082154/fullB cellshypoxiagerminal centerdifferentiationantibody-secreting cellclass switch recombination |
| spellingShingle | Jana Koers Casper Marsman Juulke Steuten Simon Tol Ninotska I. L. Derksen Anja ten Brinke S. Marieke van Ham S. Marieke van Ham Theo Rispens Oxygen level is a critical regulator of human B cell differentiation and IgG class switch recombination Frontiers in Immunology B cells hypoxia germinal center differentiation antibody-secreting cell class switch recombination |
| title | Oxygen level is a critical regulator of human B cell differentiation and IgG class switch recombination |
| title_full | Oxygen level is a critical regulator of human B cell differentiation and IgG class switch recombination |
| title_fullStr | Oxygen level is a critical regulator of human B cell differentiation and IgG class switch recombination |
| title_full_unstemmed | Oxygen level is a critical regulator of human B cell differentiation and IgG class switch recombination |
| title_short | Oxygen level is a critical regulator of human B cell differentiation and IgG class switch recombination |
| title_sort | oxygen level is a critical regulator of human b cell differentiation and igg class switch recombination |
| topic | B cells hypoxia germinal center differentiation antibody-secreting cell class switch recombination |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1082154/full |
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