The concerted change in the distribution of cell cycle phases and zone composition in germinal centers is regulated by IL-21

Dimitra Zotos, Isaak Quast, Connie S. N. Li-Wai-Suen, Craig I. McKenzie, Marcus J. Robinson, Andrey Kan, Gordon K. Smyth, Philip D. Hodgkin and David M. Tarlinton ()
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Dimitra Zotos: Monash University
Isaak Quast: Monash University
Connie S. N. Li-Wai-Suen: The Walter and Eliza Hall Institute of Medical Research
Craig I. McKenzie: Monash University
Marcus J. Robinson: Monash University
Andrey Kan: The Walter and Eliza Hall Institute of Medical Research
Gordon K. Smyth: The Walter and Eliza Hall Institute of Medical Research
Philip D. Hodgkin: The Walter and Eliza Hall Institute of Medical Research
David M. Tarlinton: Monash University

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract Humoral immune responses require germinal centres (GC) for antibody affinity maturation. Within GC, B cell proliferation and mutation are segregated from affinity-based positive selection in the dark zone (DZ) and light zone (LZ) substructures, respectively. While IL-21 is known to be important in affinity maturation and GC maintenance, here we show it is required for both establishing normal zone representation and preventing the accumulation of cells in the G1 cell cycle stage in the GC LZ. Cell cycle progression of DZ B cells is unaffected by IL-21 availability, as is the zone phenotype of the most highly proliferative GC B cells. Collectively, this study characterises the development of GC zones as a function of time and B cell proliferation and identifies IL-21 as an important regulator of these processes. These data help explain the requirement for IL-21 in normal antibody affinity maturation.

Date: 2021
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DOI: 10.1038/s41467-021-27477-0

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