Age-associated B cells are heterogeneous and dynamic drivers of autoimmunity in mice

Nickerson, Kevin M.; Smita, Shuchi; Hoehn, Kenneth B.; Marinov, Anthony; Thomas, Kayla; Kos, Justin T.; Yang, Yi; Bastacky, Sheldon; Watson, Corey T.; Kleinstein, Steven H.; Shlomchik, Mark J.

doi:10.1084/jem.20221346

Cited by 39 publications

(24 citation statements)

References 55 publications

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“…IgD-ME B cells also exhibited clonal affiliation to IgD-GC B cells and IgD-PCs and displayed a complex developmental history compatible with their clonal origin from IgD-GC B cells and clonal differentiation to IgD-PCs. This last finding echoes recent studies showing that age-associated atypical memory B cells serve as progenitors of antibody-secreting plasmablasts ( 49 ).…”

Section: Discussionsupporting

confidence: 87%

Atypical memory B cells form a pre-plasmacellular reservoir for steady-state IgD responses to common nasopharyngeal antigens

Tachó-Piñot,

Bashour,

Filipska

et al. 2023

Preprint

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The human nasopharyngeal mucosa includes organized lymphoepithelial structures continually engaged in frontline immune responses to aerodigestive antigens. Advancing our understanding of these responses might lead to the development of new strategies for the prevention and treatment of common immune disorders such as allergies. Here we identified a hitherto elusive tonsillar subset of atypical IgD class-switched IgD+IgM-memory (IgD-ME) B cells that were clonally related to IgD+IgM−germinal center (IgD-GC) B cells and IgD-secreting IgD+IgM−plasma cells (IgD-PCs) but not anergic IgD+IgM−B cells. Consistent with their pre-plasmacellular properties, IgD-ME B cells served as preferential precursors of IgD-PCs over IgD-GC B cells. IgD antibodies from IgD+IgM−cells acquired reactivity to multiple oral, airborne and commensal antigens through a mutation-dependent pathway involving both innate and adaptive signals. Thus, IgD-ME B cells may form a ready-to-use pre-plasmacellular reservoir for steady-state IgD responses likely aimed at enhancing nasopharyngeal homeostasis.One Sentence SummaryTonsillar atypical memory B cells form a ready-to-use pre-plasmacellular repertoire for IgD responses to common aerodigestive antigens.

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Section: Discussionsupporting

confidence: 87%

Atypical memory B cells form a pre-plasmacellular reservoir for steady-state IgD responses to common nasopharyngeal antigens

Tachó-Piñot,

Bashour,

Filipska

et al. 2023

Preprint

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“…Although it may not be a surprise to find expression of T-bet in Qβ + MemB because T-bet + B cells have been found to associate with a variety of physiological and pathological conditions, including viral infections ( 69 – 72 ) and the development of lupus-like symptoms ( 73 – 75 ), it is unexpected to find that T-bet deficiency affected the formation of Qβ + MemB while leaving GCB largely intact. It has been shown in this study as well as by others ( 55 , 76 ) that T-bet could be expressed at various activation stages of a B cell, not limited to memory B cells. T-bet, as a TF, could promote class-switch and regulate gene expression in B cells.…”

Section: Discussionsupporting

confidence: 78%

Antiviral memory B cells exhibit enhanced innate immune response facilitated by epigenetic memory

Zhu,

Hong,

et al. 2024

Sci. Adv.

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The long-lasting humoral immunity induced by viral infections or vaccinations depends on memory B cells with greatly increased affinity to viral antigens, which are evolved from germinal center (GC) responses. However, it is unclear whether antiviral memory B cells represent a distinct subset among the highly heterogeneous memory B cell population. Here, we examined memory B cells induced by a virus-mimicking antigen at both transcriptome and epigenetic levels and found unexpectedly that antiviral memory B cells exhibit an enhanced innate immune response, which appeared to be facilitated by the epigenetic memory that is established through the memory B cell development. In addition, T-bet is associated with the altered chromatin architecture and is required for the formation of the antiviral memory B cells. Thus, antiviral memory B cells are distinct from other GC-derived memory B cells in both physiological functions and epigenetic landmarks.

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“…Spontaneous age-dependent TLS formation has also been observed in organs such as the liver and bladder 22,23,181 . SAT cells and ABC development are observed in age-dependent TLSs in the bladder and spleen 22,180,182 and in kidneys and visceral adipose tissues in conditions that accelerate immune ageing, such as autoimmune diseases 180,183,184 and obesity 185,186 in mouse models. Studies that investigated the effects of loss of function of SAT cells and ABCs demonstrated their pathogenic potentials in these contexts 13,180,183,184,186 , which is consistent with the findings in aged, injured kidneys that are described above.…”

Section: Chronic Inflammatory Diseases and Ageingmentioning

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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Age-associated B cells are heterogeneous and dynamic drivers of autoimmunity in mice

Cited by 39 publications

References 55 publications

Atypical memory B cells form a pre-plasmacellular reservoir for steady-state IgD responses to common nasopharyngeal antigens

Atypical memory B cells form a pre-plasmacellular reservoir for steady-state IgD responses to common nasopharyngeal antigens

Antiviral memory B cells exhibit enhanced innate immune response facilitated by epigenetic memory

The roles of tertiary lymphoid structures in chronic diseases

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