2023
DOI: 10.1126/sciimmunol.add1728
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Heparan sulfate regulates IL-21 bioavailability and signal strength that control germinal center B cell selection and differentiation

Abstract: In antibody responses, mutated germinal center B (B GC ) cells are positively selected for reentry or differentiation. As the products from GCs, memory B cells and antibody-secreting cells (ASCs) support high-affinity and long-lasting immunity. Positive selection of B GC cells is controlled by signals received through the B cell receptor (BCR) and follicular helper T (T FH ) cell–derived signals, in particular costimulation through CD40. H… Show more

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Cited by 26 publications
(27 citation statements)
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References 85 publications
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“…The ability of IL-21 to synergize with CD40 in inducing S6 phosphorylation in GC B cells in vitro was further confirmed in recent studies by the Shlomchik and Yu groups ( 60 , 61 ). Notably, Dvorscek et al .…”
Section: Il-21 Promotes Gc Expansion and Shapes Gc B-cell Polarizationsupporting
confidence: 53%
See 1 more Smart Citation
“…The ability of IL-21 to synergize with CD40 in inducing S6 phosphorylation in GC B cells in vitro was further confirmed in recent studies by the Shlomchik and Yu groups ( 60 , 61 ). Notably, Dvorscek et al .…”
Section: Il-21 Promotes Gc Expansion and Shapes Gc B-cell Polarizationsupporting
confidence: 53%
“…GC with reduced or no IL-21 signaling (left) have reduced dark zone compartments and yield fewer plasma cells than GC with normal IL-21 levels (middle) ( 25 , 26 , 38 , 54 , 58 , 64 ). Elevated IL-21 levels (right) lower the B-cell positive selection threshold and allow more B-cell clones to enter the GC dark zone ( 54 , 60 , 61 ). Exacerbated IL-21 production favors GC B-cell differentiation over GC maintenance ( 61 ).…”
Section: Il-21 Promotes Gc Expansion and Shapes Gc B-cell Polarizationmentioning
confidence: 99%
“…The identification of these specific roles of IL-21 is an important mechanistic and conceptual step forward in our understanding of selection in the GC. The laboratory of D. Yu has also made similar findings about the ability of CD40 and IL-21R signals to induce c-MYC in GCBCs ( 49 ).…”
Section: Discussionmentioning
confidence: 73%
“…A recent study has provided insights into how IL-21 regulates the positive selection of GC B cells by modulating its availability and signal strength ( 13 ). Reduced IL-21 signals, possibly due to partial expression of the IL-21 receptor, can impede the differentiation of Ab-secreting PCs.…”
Section: Cytokines Produced By Tfh and Their Regulationmentioning
confidence: 99%
“…Reduced IL-21 signals, possibly due to partial expression of the IL-21 receptor, can impede the differentiation of Ab-secreting PCs. In contrast, stronger IL-21 signals, which can be achieved through exogenous IL-21 treatment, appear to favor PC differentiation and concurrently reduce the total population of GC B cells ( 13 ). Collectively, the development of GC zones as a function of time and B cell proliferation highlights IL-21 as a key regulator of these intricate processes.…”
Section: Cytokines Produced By Tfh and Their Regulationmentioning
confidence: 99%