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- Title
B cell– and T cell–intrinsic regulation of germinal centers by thymic stromal lymphopoietin signaling.
- Authors
Domeier, Phillip P.; Rahman, Ziaur S.M.; Ziegler, Steven F.
- Abstract
Long-lived and high-affinity antibodies are derived from germinal center (GC) activity, but the cytokines that regulate GC function are still being identified. Here, we show that thymic stromal lymphopoietin (TSLP) signaling regulates the GC and the magnitude of antigen-specific antibody responses. Both GC B cells and T follicular helper (TFH) cells up-regulate the expression of surface TSLP receptor (TSLPR), but cell-specific loss of TSLPR results in distinct effects on GC formation and antibody production. TSLPR signaling on T cells supports the retention of antigen-specific B cells and TFH differentiation, whereas TSLPR in B cells regulates the generation of antigen-specific memory B cells. TSLPR in both cell types promotes interferon regulatory factor 4 (IRF4) expression, which is important for efficient GC activity. Overall, we identified a previously unappreciated cytokine regulator of GCs and identified how this signaling pathway differentially regulates B and T cell responses in the GC. Germinal centers need some TSLP: Thymic stromal lymphopoietin (TSLP) promotes allergic responses within barrier tissues and is a target for therapeutic inhibition in severe asthma. The contributions of signaling through the TSLP receptor on B and T cells to germinal center (GC) antibody responses are poorly understood. Domeier et al. used mouse models lacking TSLP or its receptor to investigate how loss of TSLP signaling impairs antibody formation in GCs. Conditional deletion of the TSLP receptor in T cells impaired differentiation of T follicular helper cells that support GC B cells. However, conditional deletion of the TSLP receptor in B cells augmented antigen-specific GCs and memory B cells. These findings identify TSLP as a key cytokine utilized by both B and T cells to achieve optimal GC function. —IW
- Publication
Science Immunology, 2023, Vol 8, Issue 79, p1
- ISSN
2470-9468
- Publication type
Article
- DOI
10.1126/sciimmunol.add9413