Stromal cell control of conventional and ectopic germinal centre reactions

Silva-Cayetano, Alyssa; Linterman, Michelle A.

doi:10.1016/j.coi.2020.03.007

Cited by 13 publications

(14 citation statements)

References 83 publications

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“…Immune responses to vaccination or infection require collaborative effort from multiple types of immune cells. An exemplar of this multicellular collaboration is the generation of long‐lasting immunity by the germinal centre (GC) reaction where B cells, CD4 + helper T cells, dendritic cells, stromal cells and macrophages work together to generate antibody‐secreting plasma cells and memory B cells that protect against re‐infection (Silva‐Cayetano & Linterman, 2020; Vinuesa et al, 2016). With age, the magnitude and quality of this response declines with many of the cellular players contributing to this impairment (Eaton et al, 2004; Lefebvre et al, 2012, 2016; Lorenzo et al, 2018; Szakal et al, 1990; Turner & Mabbott, 2017a, 2017b, 2017c; Yang et al, 1996; Zheng et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Ageing promotes early T follicular helper cell differentiation by modulating expression of RBPJ

et al. 2021

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Ageing profoundly changes our immune system and is thought to be a driving factor in the morbidity and mortality associated with infectious disease in older people. We have previously shown that the impaired immunity to vaccination that occurs in aged individuals is partly attributed to the effect of age on T follicular helper (Tfh) cell formation. In this study, we examined how age intrinsically affects Tfh cell formation in both mice and humans. We show increased formation of Tfh precursors (pre‐Tfh) but no associated increase in germinal centre (GC)‐Tfh cells in aged mice, suggesting age‐driven promotion of only early Tfh cell differentiation. Mechanistically, we show that ageing alters TCR signalling which drives expression of the Notch‐associated transcription factor, RBPJ. Genetic or chemical modulation of RBPJ or Notch rescues this age‐associated early Tfh cell differentiation, and increased intrinsic Notch activity recapitulates this phenomenon in younger mice. Our data offer mechanistic insight into the age‐induced changes in T‐cell activation that affects the differentiation and ultimately the function of effector T cells.

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Section: Introductionmentioning

confidence: 99%

Ageing promotes early T follicular helper cell differentiation by modulating expression of RBPJ

et al. 2021

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“…GCs are specialized structures that conventionally form within secondary lymphoid organs, such as the spleen. In GCs, B cells undergo proliferation, hypermutation, selection, and differentiation, generating plasma cells ( 17 , 18 ). The GC response arises from the interactions between B and Tfh cells.…”

Section: Discussionmentioning

confidence: 99%

Cyclic Helix B Peptide Prolongs Skin Allograft Survival via Inhibition of B Cell Immune Responses in a Murine Model

Zheng

Wang

et al. 2021

Front. Immunol.

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Antibody-mediated rejection (AMR) represents a major cause of allograft dysfunction and results in allograft failure in solid organ transplantation. Cyclic helix B peptide (CHBP) is a novel erythropoietin-derived peptide that ameliorated renal allograft rejection in a renal transplantation model. However, its effect on AMR remains unknown. This study aimed to investigate the effect of CHBP on AMR using a secondary allogeneic skin transplantation model, which was created by transplanting skin from BALB/c mice to C57BL/6 mice with or without CHBP treatment. A secondary syngeneic skin transplantation model, involving transplantation from C57BL/6 mice to C57BL/6 mice, was also created to act as a control. Skin graft rejection, CD19+ B cell infiltration in the skin allograft, the percentages of splenic plasma cells, germinal center (GC) B cells, and Tfh cells, the serum levels of donor specific antibodies (DSAs), and NF-κB signaling in splenocytes were analyzed. Skin allograft survival was significantly prolonged in the CHBP group compared to the allogeneic group. CHBP treatment also significantly reduced the CD19+ B cell infiltration in the skin allograft, decreased the percentages of splenic plasma cells, GC B cells, and Tfh cells, and ameliorated the increase in the serum DSA level. At a molecular level, CHBP downregulated P100, RelB, and P52 in splenocytes. CHBP prolonged skin allograft survival by inhibiting AMR, which may be mediated by inhibition of NF-κB signaling to suppress B cell immune responses, thereby decreasing the DSA level.

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“…B cells with low affinity undergo apoptosis [ 35 ]. High-affinity B cells present acquired antigens to T follicular helper (T FH ) cells and receive ‘help’ from those T FH cells for immunoglobulin class switching [ 36 ]. B cells then differentiate into long-lived antibody-producing plasma cells or memory B cells or undergo apoptosis [ 36 , 37 ].…”

Section: Brc–b Cell Crosstalk During Gc Responsesmentioning

confidence: 99%

“…High-affinity B cells present acquired antigens to T follicular helper (T FH ) cells and receive ‘help’ from those T FH cells for immunoglobulin class switching [ 36 ]. B cells then differentiate into long-lived antibody-producing plasma cells or memory B cells or undergo apoptosis [ 36 , 37 ]. As demonstrated by labeling LNs from Ccl19-Cre × iDTR mice and Pdgfrb-Cre × iDTR mice, in which FRCs are depleted by treatment with diphtheria toxin (DT), FDCs arise from Pdgfrβ + perivascular precursors, and by producing IL-6 they promote SHM and IgG production; they also form a B-cell-favorable niche by producing BAFF, ICAM-1, VCAM-1, and IL-15 [ 38 , 39 ].…”

Section: Brc–b Cell Crosstalk During Gc Responsesmentioning

confidence: 99%

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Lymph node fibroblastic reticular cells steer immune responses

Abdi

et al. 2021

Trends in Immunology

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Lymph nodes (LNs), where immune responses are initiated, are organized into distinctive compartments by fibroblastic reticular cells (FRCs). FRCs imprint immune responses by supporting LN architecture, recruiting immune cells, coordinating immune cell crosstalk, and presenting antigens. Recent high-resolution transcriptional and histological analyses have enriched our knowledge of LN FRC genetic and spatial heterogeneities. Here, we summarize updated anatomic, phenotypic, and functional identities of FRC subsets, delve into topological and transcriptional remodeling of FRCs in inflammation, and illustrate the crosstalk between FRCs and immune cells. Discussing FRC functions in immunity and tolerance, we highlight state-of-the-art FRC-based therapeutic approaches for maintaining physiological homeostasis, steering protective immunity, inducing transplantation tolerance, and treating diverse immune-related diseases.

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Stromal cell control of conventional and ectopic germinal centre reactions

Cited by 13 publications

References 83 publications

Ageing promotes early T follicular helper cell differentiation by modulating expression of RBPJ

Ageing promotes early T follicular helper cell differentiation by modulating expression of RBPJ

Cyclic Helix B Peptide Prolongs Skin Allograft Survival via Inhibition of B Cell Immune Responses in a Murine Model

Lymph node fibroblastic reticular cells steer immune responses

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