Trafficking phenotype and production of granzyme B by double negative B cells (IgG+IgD−CD27−) in the elderly

Bulati, Matteo; Buffa, Silvio; Martorana, Adriana; Candore, Giuseppina; Lio, Domenico; Caruso, Calogero; Colonna‐Romano, Giuseppina

doi:10.1016/j.exger.2013.12.011

Cited by 50 publications

(45 citation statements)

References 59 publications

(91 reference statements)

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“…This was due to the increased expression of Granzyme B and FasL in IL-17A-treated B cells. Our results are consistent with previous findings that there is a subpopulation of B cells which could be stimulated to produce Granzyme B [32]. Besides, Hahne et al reported that activated B cells could express FasL, which were able to kill Fas-sensitive target cells [33].…”

Section: Discussionsupporting

confidence: 93%

IL-17A promotes migration and tumor killing capability of B cells in esophageal squamous cell carcinoma

et al. 2016

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We have previously reported that the accumulation of IL-17-producing cells could mediate tumor protective immunity by promoting the migration of NK cells, T cells and dendritic cells in esophageal squamous cell carcinoma (ESCC) patients. However, there were no reports concerning the effect of IL-17A on tumor infiltrating B cells. In this study, we investigated the accumulation of CD20+ B cells in the ESCC tumor nests and further addressed the effect of IL-17A on the migration and cytotoxicity of B cells. There was positive correlation between the levels of CD20+ B cells and IL-17+ cells. IL-17A could promote the ESCC tumor cells to produce more chemokines CCL2, CCL20 and CXCL13, which were associated with the migration of B cells. In addition, IL-17A enhanced the IgG-mediated antibody and complement mediated cytotoxicity of B cells against tumor cells. IL-17A-stimulated B cells gained more effective direct killing capability through enhanced expression of Granzyme B and FasL. The effect of IL-17A on the migration and cytotoxicity of B cells was IL-17A pathway dependent, which could be inhibited by IL-17A inhibitor. This study provides further understanding of the roles of IL-17A in humoral response, which may contribute to the development of novel tumor immunotherapy strategy.

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Section: Discussionsupporting

confidence: 93%

IL-17A promotes migration and tumor killing capability of B cells in esophageal squamous cell carcinoma

et al. 2016

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“…Indeed although DN B cells are less responsive, some particular conditions (i.e. IL-21 + ␣-IgG) can activate them [60] as demonstrated by their ability to produce Granzyme B that act against viruses or cancer cells [61,62]. Finally, the data on the expression of the inhibitory receptors CD307d and CD22 suggest that DN cells are not fully comparable to other B cell populations described in old or chronically stimulated mice and humans [23,24].…”

Section: Discussionmentioning

confidence: 97%

Double negative (CD19+IgG+IgD−CD27−) B lymphocytes: A new insight from telomerase in healthy elderly, in centenarian offspring and in Alzheimer's disease patients

et al. 2014

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a b s t r a c tImmunosenescence is characterized by the impairment of humoral immunity with changes in the memory/naive B cell compartment. In particular we have previously reported the percentage increase of a Memory IgD − CD27 − (Double Negative, DN) B cell population in aged people. In this study, we have further characterized DN B cells with the aim to better understand their contribution to immunosenescence. As DN B cells show a poor ability to proliferate in vitro, we have evaluated the expression of the inhibitory receptors CD307d and CD22 on these cells from young and old individuals. In addition we have evaluated the ability to activate DN B cells by the simultaneous use of innate (CpG) and adaptive (␣-Ig/CD40) ligands. Our data demonstrate that the refractoriness to proliferate of DN B cells does not depend on the expression of inhibitory receptors, but it is due to the kind of stimulation. Indeed, when DN B cells are stimulated engaging both BCR and TLR9, they become able to proliferate and reactivate the telomerase enzyme. In the present study, we have also compared the telomerase activity in a group of people genetically advantaged for longevity as centenarian offspring (CO) and in a group of moderate-severe Alzheimer's disease (AD) patients, who represent a model of unsuccessful aging. Our study suggests that telomerase reactivation of DN B cells, as well as their number and ability in activating, depend essentially by the biological age of the subjects studied, so the evaluation of DN B cells might allow to gain insight to healthy and unsuccessful aging.

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“…Interestingly, it has been reported in humans that granzyme B + B cells accumulated specifically in tissues and have been suggested to play a critical role in early antiviral immune responses, in the regulation of autoimmune mechanisms, and in cancer immunosurveillance (45)(46)(47). Additionally, it has recently been shown that BCR and IL-21 signaling without an efficient CD40-CD40L ligation leads to the generation of granzyme B + B cells that induce immune dysfunction in solid tumor eradication (45,(48)(49)(50) or in HIV patients (51).…”

Section: Igmmentioning

confidence: 99%

Regulatory B Cells with a Partial Defect in CD40 Signaling and Overexpressing Granzyme B Transfer Allograft Tolerance in Rodents

Durand

Huchet

Mérieau

et al. 2015

The Journal of Immunology

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Emerging knowledge regarding B cells in organ transplantation has demonstrated that these cells can no longer be taken as mere generators of deleterious Abs but can also act as beneficial players. We previously demonstrated in a rat model of cardiac allograft tolerance induced by short-term immunosuppression an accumulation in the blood of B cells overexpressing inhibitory molecules, a phenotype also observed in the blood of patients that spontaneously develop graft tolerance. In this study, we demonstrated the presence in the spleen of regulatory B cells enriched in the CD24intCD38+CD27+IgD−IgM+/low subpopulation, which are able to transfer donor-specific tolerance via IL-10 and TGF-β1–dependent mechanisms and to suppress in vitro TNF-α secretion. Following anti-CD40 stimulation, IgD−IgM+/low B cells were blocked in their plasma cell differentiation pathway, maintained high expression of the inhibitory molecules CD23 and Bank1, and upregulated Granzyme B and Irf4, two molecules described as highly expressed by regulatory B cells. Interestingly, these B cells recognized specifically a dominant donor Ag, suggesting restricted specificity that could lead to a particular B cell response. Regulatory B cells were not required for induction of tolerance and appeared following Foxp3+CD4+CD25+ regulatory T cells, suggesting cooperation with regulatory T cells for their expansion. Nevertheless, following transfer to new recipients, these B cells migrated to the allograft, kept their regulatory profile, and promoted local accumulation of Foxp3+CD4+CD25+ regulatory T cells. Mechanisms of regulatory B cells and their cell therapy potential are important to decipher in experimental models to pave the way for future developments in the clinic.

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Trafficking phenotype and production of granzyme B by double negative B cells (IgG+IgD−CD27−) in the elderly

Cited by 50 publications

References 59 publications

IL-17A promotes migration and tumor killing capability of B cells in esophageal squamous cell carcinoma

IL-17A promotes migration and tumor killing capability of B cells in esophageal squamous cell carcinoma

Double negative (CD19+IgG+IgD−CD27−) B lymphocytes: A new insight from telomerase in healthy elderly, in centenarian offspring and in Alzheimer's disease patients

Regulatory B Cells with a Partial Defect in CD40 Signaling and Overexpressing Granzyme B Transfer Allograft Tolerance in Rodents

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