Initial B Cell Activation Induces Metabolic Reprogramming and Mitochondrial Remodeling.

Area of Science:

• Immunology
• Cellular Metabolism

Background:

• B lymphocytes are crucial for adaptive immunity, producing antibodies and activating T cells.
• Understanding the metabolic support for naive B cell activation is vital for effective immune responses.

Purpose of the Study:

• To investigate how global metabolism supports naive B cell activation.
• To elucidate carbon utilization and mitochondrial dynamics during the initial stages of a humoral immune response.

Main Methods:

• Coupling RNA sequencing (RNA-seq) with glucose isotopomer tracing.
• Analyzing metabolic pathways including oxidative phosphorylation (OXPHOS), the tricarboxylic acid (TCA) cycle, and nucleotide biosynthesis.
• Assessing the impact of glucose restriction, OXPHOS inhibition, and glutamine restriction on B cell functions.

Main Results:

• Stimulated B cells upregulate OXPHOS, TCA cycle, and nucleotide biosynthesis, but not glycolysis.
• Glucose primarily supports ribonucleotide biosynthesis, with minimal contribution to the TCA cycle.
• Inhibition of OXPHOS or glutamine restriction significantly impairs B cell growth and differentiation.
• B cell activation involves extensive mitochondrial remodeling.

Conclusions:

• Naive B cell activation is metabolically supported by OXPHOS and nucleotide synthesis, with distinct roles for glucose and glutamine.
• Metabolic adaptation, including mitochondrial dynamics, is critical for initiating a humoral immune response.