Metabolic determinants of B-cell selection.
Biochem Soc Trans
; 49(3): 1467-1478, 2021 06 30.
Article
em En
| MEDLINE
| ID: mdl-34196360
ABSTRACT
B-cells are antibody-producing cells of the adaptive immune system. Approximately 75% of all newly generated B-cells in the bone marrow are autoreactive and express potentially harmful autoantibodies. To prevent autoimmune disease, the immune system has evolved a powerful mechanism to eliminate autoreactive B-cells, termed negative B-cell selection. While designed to remove autoreactive clones during early B-cell development, our laboratory recently discovered that transformed B-cells in leukemia and lymphoma are also subject to negative selection. Indeed, besides the risk of developing autoimmune disease, B-cells are inherently prone to malignant transformation to produce high-affinity antibodies, B-cells undergo multiple rounds of somatic immunoglobulin gene recombination and hypermutation. Reflecting high frequencies of DNA-breaks, adaptive immune protection by B-cells comes with a dramatically increased risk of development of leukemia and lymphoma. Of note, B-cells exist under conditions of chronic restriction of energy metabolism. Here we discuss how these metabolic gatekeeper functions during B-cell development provide a common mechanism for the removal of autoreactive and premalignant B-cells to safeguard against both autoimmune diseases and B-cell malignancies.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Autoanticorpos
/
Doenças Autoimunes
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Linfócitos B
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Autoimunidade
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Imunidade Adaptativa
Limite:
Animals
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Humans
Idioma:
En
Revista:
Biochem Soc Trans
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos