Vanderbilt Univ, Dept Pathol Microbiol & Immunol, Med Ctr, 1161 21st Ave South, AA 4214 B MCN, Nashville, TN 37232 - USA
 Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Sao Paulo - Brazil
 Univ Sao Paulo, Dept Immunol, BR-05508000 Sao Paulo - Brazil
Total Affiliations: 4
JOURNAL OF IMMUNOLOGY;
DEC 1 2020.
Web of Science Citations:
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)