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Second signals rescue B cells from activation-induced mitochondrial dysfunction and death
Munir Akkaya1, Javier Traba2, Alexander S Roesler3,4
1Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA. munir.akkaya@nih.gov.
Nature Immunology
|July 11, 2018
Summary
B cells rapidly boost metabolism upon antigen binding. Without a second signal, B cells lose mitochondrial function and undergo apoptosis within 9 hours, highlighting a critical survival window.
Area of Science:
- Immunology
- Cell Biology
- Metabolic pathways
Background:
- B cell activation requires antigen binding to the B cell antigen receptor (BCR) and a second signal from helper T cells.
- The metabolic requirements and fate of B cells in the absence of a second signal are not fully understood.
Purpose of the Study:
- To investigate the metabolic response of B cells to antigen stimulation.
- To determine the consequences of lacking a second signal on B cell viability and mitochondrial function.
Main Methods:
- Measurement of metabolic activity, including oxidative phosphorylation and glycolysis, in B cells after antigen stimulation.
- Assessment of mitochondrial function and B cell apoptosis.
- Investigation of the role of intracellular calcium and TLR9 signaling in B cell survival.
Main Results:
- B cells significantly increased metabolic activity (oxidative phosphorylation and glycolysis) upon BCR engagement.
- Absence of a second signal led to progressive loss of mitochondrial function and glycolytic capacity.
- Mitochondrial dysfunction resulted from calcium accumulation, which was preventable by T cell help or TLR9 signaling for approximately 9 hours post-antigen binding.
Conclusions:
- BCR signaling initiates a time-limited metabolic program for B cell survival.
- B cells require a second signal within a defined window to prevent metabolic collapse and apoptosis.
- Intracellular calcium regulation is critical for maintaining B cell metabolic function and viability.
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