Aging Converts Innate B1a Cells into Potent CD8+ T Cell Inducers

Lee-Chang, Catalina; Bodogai, Monica; Moritoh, Kanako; Chen, Xin; Wersto, Robert P.; Sen, Ranjan; Young, Howard A.; Croft, Michael; Ferrucci, Luigi; Biragyn, Arya

doi:10.4049/jimmunol.1502034

Cited by 31 publications

(47 citation statements)

References 75 publications

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“…Meanwhile, the productions of IFN‐γ and TNF‐α were downregulated in the 4‐1BBL+ B cell group, indicating a negative regulatory role for cellular immunity. Interestingly, our data were not consistent with other studies, in which 4‐1BBL+ B cells could induce GrB+ CD8+ T cells and increase the proliferation of antigen‐specific CD8+ T cells . However, in our study, the 4‐1BBL+ B cells could increase cytokine secretion of IL‐2, IL‐4, and IL‐6.…”

Section: Discussioncontrasting

confidence: 99%

“…Interestingly, our data were not consistent with other studies, in which 4-1BBL+ B cells could induce GrB+ CD8+ T cells and increase the proliferation of antigen-specific CD8+ T cells. 17,37 However, in our study,…”

Section: Discussioncontrasting

confidence: 62%

“…Lee‐Chang et al reported an elevated expression of 4‐1BB (CD137) ligand (4‐1BBL) on B cells with increasing age and immune reconstitution after chemotherapy and autologous progenitor cell transplantation in humans. The 4‐1BB is a costimulatory member of the tumor necrosis factor receptor family expressed on activated T cells .…”

Section: Introductionmentioning

confidence: 99%

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HBcAg‐induced upregulated 4‐1BB ligand on B cells contributes to B‐cell hyperactivation during chronic hepatitis B infection

Liu

Wang

Chen

et al. 2019

Journal of Medical Virology

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During the natural history of chronic hepatitis B infection (CHB), the function of B cells is still obscure. Several limited studies have suggested that B cells are highly active in patients with CHB. In the present study, we reported that the 4‐1BB ligand (4‐1BBL) expression on B cells was significantly higher in patients with CHB than that in healthy subjects, meanwhile, the patients with CHB had higher serological IgG levels. Further, after being stimulated with sCD40L or hepatitis B core antigen (HBcAg), B cells had higher levels of 4‐1BBL. After being cocultured with 4‐1BBL+ B cells, the expressions of CD69 and 4‐1BB on CD4+ T cells were significantly higher than that cocultured with 4‐1BB− B cells. Cytokines including interleukin (IL)‐2, IL‐4, and IL‐6 were significantly higher in the supernatant from 4‐1BBL+ B cells coculture group than those from coculture group of 4‐1BBL− B cell group, respectively; while IFN‐γ and TNF‐α in cocultured supernatant of 4‐1BBL+ B cell group were significantly lower. Consistently, the total IgG levels in culture supernatant were significantly higher in 4‐1BBL+ B cell group. Thus, hyperactive status of B cells in patients with CHB could be partially derived from the higher 4‐1BBL expression on B cells triggered by HBcAg. 4‐1BBL signaling pathway is involved in B cells activation, and further regulates B cell‐T cell interaction by modulating the cytokines secretion, which might be critical in B cells dysfunction during CHB infection.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussioncontrasting

confidence: 62%

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HBcAg‐induced upregulated 4‐1BB ligand on B cells contributes to B‐cell hyperactivation during chronic hepatitis B infection

Liu

Wang

Chen

et al. 2019

Journal of Medical Virology

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“…This may be as a result of their role as antigen-presenting cells, thus aiding the tumor-infiltrating T cells, or may be a function dependent on their antibody (Nelson 2010;Lee-Chang et al 2014). It is interesting to note that the age-associated 4-1BBL+ B cells make excellent antigen-presenting cells that can activate CD8+ T cells and therefore stimulate antitumor activity (Lee-Chang et al 2016). B cell infiltrates may be diffused or aggregated into tertiary lymphoid structures, in some cases recapitulating germinal center morphology.…”

Section: Role Of B Cells In Antitumor Activitymentioning

confidence: 99%

Older Human B Cells and Antibodies

Dunn-Walters¹,

O’Hare²

2017

Handbook of Immunosenescence

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B cells have a number of different roles in the immune response. Their excellent antigen presentation potential can contribute to the activation of other cells of the immune system, and evidence is emerging that specialized subsets of these cells, that may be increased with age, can influence the cell-mediated immune system in antitumor responses. They can also regulate immune responses, to avoid autoreactivity and excessive inflammation. Deficiencies in regulatory B cells may be beneficial in cancer but will only exacerbate the inflammatory environment that is a hallmark of aging. The B cell role as antibody producers is particularly important, since antibodies perform numerous different functions in different environments. Although studying tissue responses in humans is not as easy as in mice, we do know that certain classes of antibodies are more suited to protecting the mucosal tissues (IgA) or responding to T-independent bacterial polysaccharide antigens (IgG2) so we can make some inference with respect to tissue-specific immunity from a study of peripheral blood. We can also make inferences about changes in B cell development with age by looking at the repertoire of different B cell populations to see how age affects the selection events that would normally occur to avoid autoreactivity, or increase specificity, to antigen

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“…It has been reported in the literature in mice that both B-1 and B-2 cells have the capability to also aid in antigen presentation (Lee-Chang et al, 2016;Popi et al, 2016). A future goal in our lab is to determine whether or not this ability is retained within the reptilian B cell.…”

Section: │ Discussionmentioning

confidence: 94%

Out of the Shell: Exploring The Phagocytic Capabilities of the B Cell and Isolated Lymphoid Follicle-lie Structures in the Red-Eared Slider, Trachemys Scripta

Ashford¹

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I would first like to thank both of my Co-PIs, Dr. Laura Vogel and Dr. Rachel Bowden for giving me the opportunity to work with them on this wonderful journey into the realm of research and turtles. This work would not have been possible without their endless amounts of support and encouragement. The door to their offices were always open whenever I ran into trouble in the lab or had a question about my research or writing. Secondly, I would like to thank all of my past and present lab members for their contributions both in the lab and out in the field;

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Aging Converts Innate B1a Cells into Potent CD8+ T Cell Inducers

Cited by 31 publications

References 75 publications

HBcAg‐induced upregulated 4‐1BB ligand on B cells contributes to B‐cell hyperactivation during chronic hepatitis B infection

HBcAg‐induced upregulated 4‐1BB ligand on B cells contributes to B‐cell hyperactivation during chronic hepatitis B infection

Older Human B Cells and Antibodies

Out of the Shell: Exploring The Phagocytic Capabilities of the B Cell and Isolated Lymphoid Follicle-lie Structures in the Red-Eared Slider, Trachemys Scripta

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