AMPK alpha 1 in B Cells Dampens Primary Antibody Responses yet Promotes Mitochondrial Homeostasis and Persistence of B Cell Memory

Autor(es)

Brookens, Shawna K. ^[1] ; Cho, Sung Hoon ^[2] ; Basso, Paulo J. ^{[3, 4]} ; Boothby, Mark R. ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Vanderbilt Univ, Dept Canc Biol, Nashville, TN 37232 - USA

^[2] Vanderbilt Univ, Dept Pathol Microbiol & Immunol, Med Ctr, 1161 21st Ave South, AA 4214 B MCN, Nashville, TN 37232 - USA

^[3] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Dept Immunol, BR-05508000 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF IMMUNOLOGY; v. 205, n. 11, p. 3011+, DEC 1 2020.
• Citações Web of Science: 0

Resumo

Emerging evidence indicates that metabolic programs regulate B cell activation and Ab responses. However, the metabolic mediators that support the durability of the memory B cell and long-lived plasma cell populations are not fully elucidated. Adenosine monophosphate-activated protein kinase (AMPK) is an evolutionary conserved serine/threonine kinase that integrates cellular energy status and nutrient availability to intracellular signaling and metabolic pathways. In this study, we use genetic mouse models to show that loss of AMPK alpha 1 in B cells led to a weakened recall Ab response associated with a decline in the population of memory-phenotype B cells. AMPK alpha 1-deficient memory B lymphocytes exhibited aberrant mitochondrial activity, decreased mitophagy, and increased lipid peroxidation. Moreover, loss of AMPK alpha 1 in B lymphoblasts was associated with decreased mitochondrial spare respiratory capacity. Of note, AMPK alpha 1 in B cells was dispensable for stability of the bone marrow-resident, long-lived plasma cell population, yet absence of this kinase led to increased rates of Ig production and elevated serum Ab concentrations elicited by primary immunization. Collectively, our findings fit a model in which AMPK alpha 1 in B cells supports recall function of the memory B cell compartment by promoting mitochondrial homeostasis and longevity but restrains rates of Ig production. (AU)

• Processo FAPESP: 18/08563-8 - Nuetrientes e Metabolismo na regulação da imunidade humoral: O papel dos HIFs
• Beneficiário: Paulo José Basso
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado