“An Intrinsic Program Determines Key Age-Associated Changes in Adaptive Immunity That Limit Response to Non-Pathogens”

Swain, Susan L.; Kugler‐Umana, Olivia; Tonkonogy, Susan L.

doi:10.3389/fragi.2021.701900

Cited by 5 publications

(14 citation statements)

References 51 publications

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“…The studies in GF mice as well as their phenotype, provides strong evidence that IgD + ABC are a naïve subset that develops as part of an age-associated intrinsic developmental pathway (Swain et al 2021). It is not clear whether the development of the IgD - ABC subsets during aging, depends on self-Ag recognition though there are studies indicating that the CD21 - CD23 - ABC in unimmunized SPF mice have undergone some affinity maturation compared to FOB (Russell Knode et al 2017), suggesting that they do contain some Ag-experienced B cells.…”

Section: Discussionmentioning

confidence: 99%

“…Our studies do not rule out a role of cell-intrinsic TLR signaling in IgD + ABC activation, but we predict they play a role given the previous studies (Hua & Hou 2013; Fillatreau et al 2020). We postulate that high dependence of the ABC response on both TLR7 and TLR9, and on cell-extrinsic endosomal TLR expression, limits their response to those stimulated by pathogens that provide strong stimulation to viral sensing PR pathways (Kugler-Umana et al 2020; Swain et al 2021). In general, we suggest this serves as an evolutionary strategy to prevent unnecessary inflammation and the development of autoimmunity in the aged (Swain et al 2021).…”

Section: Discussionmentioning

confidence: 99%

“…The immune system undergoes many changes with age that contribute to reduced responses to infections and to immunizations (Frasca & Blomberg 2020; Shaw et al 2013; Swain et al 2021). Responses mediated by innate cells are reduced (Wong et al 2017; Bupp et al 2018; Shaw et al 2013; Pillai et al 2016) with age.…”

Section: Introductionmentioning

confidence: 99%

“…The immune system undergoes many changes with age that contribute to reduced responses to infections and to immunizations (Frasca & Blomberg 2020;Shaw et al 2013;Swain et al 2021).…”

Section: Introductionmentioning

confidence: 99%

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IgD⁺ Age-Associated B cells are the progenitors of the main T-independent B cell response to infection that generates protective Ab and can be induced by an inactivated vaccine in the aged

Kugler‐Umana

Zhang

Kuang

et al. 2022

Preprint

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Age-associated B cells (ABC) accumulate with age and are associated with autoimmunity and chronic infection. However, their contributions to acute infection in the aged and their developmental pathways are unclear. We find that the response against influenza A virus infection in aged mice is dominated by a Fas+GL7- effector B cell population we call infection-induced-ABC (iABC). Most iABC express IgM and include antibody-secreting cells in the spleen, lung and bone marrow. We find that in response to influenza, IgD+CD21-CD23-ABC are the precursors of iABC. These IgD+ABC develop in germ free mice, so are independent of foreign antigen recognition, suggesting they arise from an intrinsic age-associated developmental program. The response of ABC to influenza infection, resulting in iABC, is T cell independent and requires both extrinsic TLR7 and TLR9 signals. In response to influenza infection, IgD+ABC can induce a faster recovery of weight and higher total anti-influenza IgG and IgM titers that can neutralize virus. Immunization with whole inactivated virus also generates iABC in aged mice. Thus, in unimmunized aged mice, whose other B and T cell responses have waned, IgD+ABC are likely the na&iumlve B cells with the potential to become Ab-secreting cells and to provide protection from infection in the aged.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…The immune system undergoes many changes with age that contribute to reduced responses to infections and to immunizations (Frasca & Blomberg 2020;Shaw et al 2013;Swain et al 2021).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

IgD⁺ Age-Associated B cells are the progenitors of the main T-independent B cell response to infection that generates protective Ab and can be induced by an inactivated vaccine in the aged

Kugler‐Umana

Zhang

Kuang

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…The immune system undergoes many changes with age that contribute to reduced responses to infections and to immunizations (Frasca & Blomberg, 2020;Shaw et al, 2013;Swain et al, 2021).…”

mentioning

confidence: 99%

IgD⁺age‐associated B cells are the progenitors of the main T‐independent B cell response to infection that generates protective Ab and can be induced by an inactivated vaccine in the aged

et al. 2022

Self Cite

View full text Add to dashboard Cite

Age‐associated B cells (ABC) accumulate with age and are associated with autoimmunity and chronic infection. However, their contributions to acute infection in the aged and their developmental pathways are unclear. We find that the response against influenza A virus infection in aged mice is dominated by a Fas+GL7− effector B cell population we call infection‐induced ABC (iABC). Most iABC express IgM and include antibody‐secreting cells in the spleen, lung, and bone marrow. We find that in response to influenza, IgD+CD21−CD23−ABC are the precursors of iABC and become memory B cells. These IgD+ABC develop in germ‐free mice, so are independent of foreign antigen recognition. The response of ABC to influenza infection, resulting in iABC, is T cell independent and requires both extrinsic TLR7 and TLR9 signals. In response to influenza infection, IgD+ABC can induce a faster recovery of weight and higher total anti‐influenza IgG and IgM titers that can neutralize virus. Immunization with whole inactivated virus also generates iABC in aged mice. Thus, in unimmunized aged mice, whose other B and T cell responses have waned, IgD+ABC are likely the naive B cells with the potential to become Ab‐secreting cells and to provide protection from infection in the aged.

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Changes of B cell subsets in different types of diabetes and its effect on the progression of latent autoimmune diabetes in adults

Wu,

Song,

Chen

et al. 2023

Endocrine

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Developmental abnormalities in B cells is one of the key players in autoimmune diabetes, but little is known about its role in latent autoimmune diabetes in adults (LADA). This study aimed to investigate the distribution of B cell subsets in different types of diabetes and to analyze their correlations with other biochemical parameters. MethodsA total of 140 participants were prospectively enrolled from January 2021 to December 2022. Diabetes-related autoantibodies and laboratory indicators were tested. Flow cytometry was used to analyze the percentage of circulating B cell subsets and T follicular cells.The correlation of B cell subsets with different indicators was assessed by Spearman's correlation method. ResultsWe observed that the Naïve phenotype cells tended to be less frequent in patients with diabetes than in healthy controls. The frequency of plasmablasts (PB) and Breg cell-related phenotype (B10) were signi cantly higher in LADA. Notably, the percentage of PB was positively associated with levels of islet cell antibody (ICA) and insulin autoantibody (IAA), but inversely associated with fasting Cpeptide (FCP), further indicating that PB may promote the destruction of β-cell in patients with diabetes. ConclusionsThis study showed that patients with LADA had a signi cantly altered B cell repertoires, especially exhibiting a naive to memory phenotype shift. Our study provided valuable information on the distribution characteristics of B cell subsets in LADA and suggested the feasibility of B-cell targeted therapy in LADA patients.

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“An Intrinsic Program Determines Key Age-Associated Changes in Adaptive Immunity That Limit Response to Non-Pathogens”

Cited by 5 publications

References 51 publications

IgD⁺ Age-Associated B cells are the progenitors of the main T-independent B cell response to infection that generates protective Ab and can be induced by an inactivated vaccine in the aged

IgD⁺ Age-Associated B cells are the progenitors of the main T-independent B cell response to infection that generates protective Ab and can be induced by an inactivated vaccine in the aged

IgD⁺age‐associated B cells are the progenitors of the main T‐independent B cell response to infection that generates protective Ab and can be induced by an inactivated vaccine in the aged

Changes of B cell subsets in different types of diabetes and its effect on the progression of latent autoimmune diabetes in adults

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“An Intrinsic Program Determines Key Age-Associated Changes in Adaptive Immunity That Limit Response to Non-Pathogens”

Cited by 5 publications

References 51 publications

IgD+ Age-Associated B cells are the progenitors of the main T-independent B cell response to infection that generates protective Ab and can be induced by an inactivated vaccine in the aged

IgD+ Age-Associated B cells are the progenitors of the main T-independent B cell response to infection that generates protective Ab and can be induced by an inactivated vaccine in the aged

IgD+age‐associated B cells are the progenitors of the main T‐independent B cell response to infection that generates protective Ab and can be induced by an inactivated vaccine in the aged

Changes of B cell subsets in different types of diabetes and its effect on the progression of latent autoimmune diabetes in adults

Contact Info

Product

Resources

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IgD⁺ Age-Associated B cells are the progenitors of the main T-independent B cell response to infection that generates protective Ab and can be induced by an inactivated vaccine in the aged

IgD⁺ Age-Associated B cells are the progenitors of the main T-independent B cell response to infection that generates protective Ab and can be induced by an inactivated vaccine in the aged

IgD⁺age‐associated B cells are the progenitors of the main T‐independent B cell response to infection that generates protective Ab and can be induced by an inactivated vaccine in the aged