Mitochondrial function is essential for humoral immunity by controlling flux of the TCA cycle, phosphatidic acid and mTOR activity in B cells

• DOI: 10.1101/2021.01.14.426649
• Publication Date: 2021-01-17T04:50:14Z
• Authors: Sophia Urbanczyk; Olivier R. Baris; Jörg Hofmann; Florian Golombek; Kathrin Castiglione; Xianyi Meng; Aline Bozec; Dimitrios Mougiak...; Sebastian R. Schulz; Wolfgang Schuh; Ursula Schlötzer-...; Tobit D. Steinmetz; Susanne Brodesser; Rudolf J. Wiesner; Dirk Mielenz
• Keywords: 0303 health sciences; 03 medical and health sciences; [SDV]Life Sciences [q-bio]

Abstract The function of mitochondrial respiration during B cell fate decisions and differentiation remains equivocal. This study reveals that selection for fitness occurs activation is essential subsequent plasma differentiation. By expressing a mutated helicase in transitional cells, we depleted DNA maturation, resulting reduced oxidative phosphorylation. Although no changes follicular development were evident, germinal centers, class switch recombination to IgG, generation humoral immunity diminished. Defective phosphorylation led aberrant flux the tricarboxylic acid cycle lowered amount saturated phosphatidic acid. Consequently, MTOR activity BLIMP-1 induction curtailed whereas HIF1α, glycolysis AMPK amplified. Exogenous increased mTOR activated cells. Hence, required selected cells successful functional