Metabolic Reprogramming Commits Differentiation of Human CD27+IgD+ B Cells to Plasmablasts or CD27−IgD− Cells

Torigoe, Masataka; Iwata, S.; Nakayamada, Shingo; Sakata, Kimio; Zhang, Mingzeng; Hajime, Maiko; Miyazaki, Yusuke; Narisawa, Manabu; Ishii, Koji; Shibata, Hirotaka

doi:10.4049/jimmunol.1601908

Cited by 81 publications

(52 citation statements)

References 62 publications

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“…93 While metabolic pathways in memory T cells have been studied extensively, memory B cell metabolism remains largely unexplored with a few recent exceptions. 97 It is possible that these functional differences are caused by enhanced sensitivity to toll-like receptor ligands by memory B cells. Memory B cells deficient in the autophagy gene ATG7 are present in normal numbers initially after immunization or infection with influenza, but then wane rapidly.…”

Section: Memory B Cellsmentioning

confidence: 99%

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Plasma cells: You are what you eat

D'Souza

Bhattacharya

2019

Immunological Reviews

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Summary Plasma cells are terminally differentiated B lymphocytes that constitutively secrete antibodies. These antibodies can provide protection against pathogens, and their quantity and quality are the best clinical correlates of vaccine efficacy. As such, plasma cell lifespan is the primary determinant of the duration of humoral immunity. Yet dysregulation of plasma cell function can cause autoimmunity or multiple myeloma. The longevity of plasma cells is primarily dictated by nutrient uptake and non‐transcriptionally regulated metabolic pathways. We have previously shown a positive effect of glucose uptake and catabolism on plasma cell longevity and function. In this review, we discuss these findings with an emphasis on nutrient uptake and its effects on respiratory capacity, lifespan, endoplasmic reticulum stress, and antibody secretion in plasma cells. We further discuss how some of these pathways may be dysregulated in multiple myeloma, potentially providing new therapeutic targets. Finally, we speculate on the connection between plasma cell intrinsic metabolism and systemic changes in nutrient availability and metabolic diseases.

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Section: Memory B Cellsmentioning

confidence: 99%

“…Compared with naive B cells, this led to enhanced differentiation by memory B cells into plasmablasts. 97 It is possible that these functional differences are caused by enhanced sensitivity to toll-like receptor ligands by memory B cells.…”

Section: Memory B Cellsmentioning

confidence: 99%

Plasma cells: You are what you eat

D'Souza

Bhattacharya

2019

Immunological Reviews

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“…In the Roquin mouse model of lupus, activation of AMPK and inhibition of mTOR limited B cell differentiation into GC B and plasma cells, which was associated with a reduced disease activity [27]. In SLE patients, high mTOR activation in CD19 + B cells correlates with plasmablast numbers and disease activity [28] (Fig. 2).…”

Section: Review Series: Translating Immunometabolismmentioning

confidence: 99%

Immune cell metabolism in autoimmunity

Teng

Cornaby

et al. 2019

Clinical and Experimental Immunology

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Immune metabolism is a rapidly moving field. While most of the research has been conducted to define the metabolism of healthy immune cells in the mouse, it is recognized that the overactive immune system that drives autoimmune diseases presents metabolic abnormalities that provide therapeutic opportunities, as well as a means to understand the fundamental mechanisms of autoimmune activation more clearly. Here, we review recent publications that have reported how the major metabolic pathways are affected in autoimmune diseases, with a focus on rheumatic diseases. mental Immunology 2019, 197: 141-142. T cell metabolism in chronic viral infection. Clinical and Experimental Immunology 2019, 197: 143-152. Sculpting tumor microenvironment with immune system: from immunometabolism to immunoediting. Clinical and Experimental Immunology 2019, 197: 153-160. Sensing between reactions -how the metabolic microenvironment shapes immunity. Clinical and Experimental Immunology 2019, 197: 161-169. Altered metabolic pathways regulate synovial inflammation in rheumatoid arthritis. OTHER ARTICLES PUBLISHED IN THIS REVIEW SERIES Translating immunometabolism: towards curing human diseases by targeting metabolic processes underpinning the immune response. Clinical and Experi

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“…In addition to CD4 + T cells, mTOR is overactivated in the B cells of SLE patients, and it correlates with plasmablast numbers and disease activity. 27 In the Roquin san/san lupus-prone mouse, treatment with either metformin or rapamycin inhibited B cell differentiation into GC B and plasma cells, and reduced disease activity, which implicated the AMPK/mTOR pathway in the activation of autoreactive B cells. 25 These results also suggest that a high basal level of mTOR activation may set a lower threshold for B cell activation and differentiation, although neither study in SLE patients or in the Roquin san/san mice could distinguish B-cell intrinsic mTOR activation.…”

Section: Mtor Ac Tivati On In Lupusmentioning

confidence: 99%

Metabolic determinants of lupus pathogenesis

Teng

Brown

Choi

et al. 2020

Immunological Reviews

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The metabolism of healthy murine and more recently human immune cells has been investigated with an increasing amount of details. These studies have revealed the challenges presented by immune cells to respond rapidly to a wide variety of triggers by adjusting the amount, type, and utilization of the nutrients they import. A concept has emerged that cellular metabolic programs regulate the size of the immune response and the plasticity of its effector functions. This has generated a lot of enthusiasm with the prediction that cellular metabolism could be manipulated to either enhance or limit an immune response. In support of this hypothesis, studies in animal models as well as human subjects have shown that the dysregulation of the immune system in autoimmune diseases is associated with a skewing of the immunometabolic programs. These studies have been mostly conducted on autoimmune CD4 + T cells, with the metabolism of other immune cells in autoimmune settings still being understudied. Here we discuss systemic metabolism as well as cellular immunometabolism as novel tools to decipher fundamental mechanisms of autoimmunity. We review the contribution of each major metabolic pathway to autoimmune diseases, with a focus on systemic lupus erythematosus (SLE), with the relevant translational opportunities, existing or predicted from results obtained with healthy immune cells. Finally, we review how targeting metabolic programs may present novel therapeutic venues. K E Y W O R D Sglucose, glutamine, lupus, metabolic inhibitors, metabolism

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Metabolic Reprogramming Commits Differentiation of Human CD27+IgD+ B Cells to Plasmablasts or CD27−IgD− Cells

Cited by 81 publications

References 62 publications

Plasma cells: You are what you eat

Plasma cells: You are what you eat

Immune cell metabolism in autoimmunity

Metabolic determinants of lupus pathogenesis

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