T cell help in the autoreactive germinal center

Akama-Garren, Elliot H.; Carroll, Michael

doi:10.1111/sji.13192

Cited by 4 publications

(3 citation statements)

References 467 publications

(827 reference statements)

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“…By contrast, autoreactive B cells can enter the follicular niche, receive survival factors and survive in TLSs 33 . In autoimmunity, disease-specific autoantibodies are produced in TLSs in target organs 34,35 . Autoantibody production in TLSs has also been reported in aged, injured kidneys 20 .…”

Section: Characteristics Of Tlss and Slosmentioning

confidence: 99%

The roles of tertiary lymphoid structures in chronic diseases

et al. 2023

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Tertiary lymphoid structures (TLSs) are ectopic lymphoid tissues that drive antigen-specific immune responses at sites of chronic inflammation. Unlike secondary lymphoid organs such as lymph nodes, TLSs lack capsules and have their own unique characteristics and functions. The presumed influence of TLSs on the disease course has led to widespread interest in obtaining a better understanding of their biology and function. Studies using single-cell analyses have suggested heterogeneity in TLS composition and phenotype, and consequently, functional correlates with disease progression are sometimes conflicting. The presence of TLSs correlates with a favourable disease course in cancer and infection. Conversely, in autoimmune diseases and chronic age-related inflammatory diseases including chronic kidney disease, the presence of TLSs is associated with a more severe disease course. However, the detailed mechanisms that underlie these clinical associations are not fully understood. To what extent the mechanisms of TLS development and maturation are shared across organs and diseases is also still obscure. Improved understanding of TLS development and function at the cellular and molecular levels may enable the exploitation of these structures to improve therapies for chronic diseases, including chronic kidney disease.• In autoimmunity, chronic inflammation and ageing, the presence of TLSs correlates with pathological conditions and a more severe disease course.• Functional characterization of TLSs in human diseases and the development of interventions to induce or reduce TLSs could lead to promising therapeutic avenues.Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author selfarchiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

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Section: Characteristics Of Tlss and Slosmentioning

confidence: 99%

The roles of tertiary lymphoid structures in chronic diseases

et al. 2023

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“…There is increasing evidence that Tfh cells may indeed play a central role in this disease, according to analyses of NMO patients ( 12 ) and a murine model of the disease ( 13 ). The emergence of Tfh cells as a key player in this autoantibody-mediated disorder is not surprising, given their central contribution to B cell selection, differentiation, and affinity maturation against both foreign and self-antigens and role in the loss of B cell tolerance ( 14 , 15 ). Indeed, a recent analysis of the TCR repertoire of self-reactive CD4 + T cells has revealed that autoreactive clones mainly express a Tfh or Tfh-like helper phenotype ( 16 ).…”

Section: T Helper Subsets and Autoimmune Diseasementioning

confidence: 99%

Renegade T cell clones and autoimmune disease

Cantor

2023

Proc. Natl. Acad. Sci. U.S.A.

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“…Peripheral B cell tolerance is maintained in the GC through mechanisms such as clonal redemption and clonal anergy ( 1 – 7 ), but failures in these mechanisms can lead to production of pathogenic, class-switched, and epitope-spread autoantibodies ( 8 – 10 ). Although the function of follicular T cells, including T follicular helper (T FH ) and T follicular regulatory (T FR ) cells, has been well characterized in the normal GC ( 11 , 12 ), the role of these cells in the autoreactive GC is less well understood ( 13 – 15 ).…”

Section: Introductionmentioning

confidence: 99%

T cell help shapes B cell tolerance

Akama-Garren,

Yin,

Prestwood

et al. 2024

Sci. Immunol.

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T cell help is a crucial component of the normal humoral immune response, yet whether it promotes or restrains autoreactive B cell responses remains unclear. Here, we observe that autoreactive germinal centers require T cell help for their formation and persistence. Using retrogenic chimeras transduced with candidate TCRs, we demonstrate that a follicular T cell repertoire restricted to a single autoreactive TCR, but not a foreign antigen–specific TCR, is sufficient to initiate autoreactive germinal centers. Follicular T cell specificity influences the breadth of epitope spreading by regulating wild-type B cell entry into autoreactive germinal centers. These results demonstrate that TCR-dependent T cell help can promote loss of B cell tolerance and that epitope spreading is determined by TCR specificity.

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T cell help in the autoreactive germinal center

Cited by 4 publications

References 467 publications

The roles of tertiary lymphoid structures in chronic diseases

The roles of tertiary lymphoid structures in chronic diseases

Renegade T cell clones and autoimmune disease

T cell help shapes B cell tolerance

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