Redox remodeling allows and controls B-cell activation and differentiation.
Roberta Vené1, Laura Delfino, Patrizia Castellani
1National Cancer Research Institute, Genova, Italy.
B cell differentiation into antibody-secreting plasma cells involves significant redox changes, including reactive oxygen species (ROS) production and antioxidant responses. These redox shifts are crucial for B cell activation, differentiation, and antibody secretion, occurring both in vitro and in vivo.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- B lymphocyte differentiation into plasma cells involves substantial metabolic, structural, and functional alterations.
- Redox homeostasis plays a critical role in cellular processes, including immune cell function.
Purpose of the Study:
- To investigate the intra- and extracellular redox changes during B lymphocyte differentiation.
- To determine the role of reactive oxygen species (ROS) and antioxidant responses in B cell activation and antibody production.
Main Methods:
- Lipopolysaccharide (LPS)-induced differentiation of murine B splenocytes in vitro.
- Measurement of ROS production, antioxidant molecule expression (thioredoxin, xCT), and thiol release (glutathione, cysteine).
- Inhibition of NADPH oxidase and addition of reducing agents (2-ME) to assess functional impacts.
- Histological analysis of spleen sections from immunized mice.
Main Results:
- LPS stimulation increased ROS production and triggered a robust antioxidant response, including thioredoxin and xCT upregulation, and glutathione/cysteine release.
- Early ROS production via NADPH oxidase is essential for B cell activation and differentiation.
- Reducing agents enhanced IgM secretion, indicating a functional role for the antioxidant response.
- In vivo studies confirmed similar redox modifications in spleen tissues during immune responses.
Conclusions:
- B cell differentiation is characterized by significant redox modifications, including ROS generation and antioxidant defenses.
- Redox changes are integral to B cell activation, differentiation, and antibody secretion, impacting both cellular processes and immune function.
- The observed in vitro redox dynamics are relevant to in vivo physiological immune responses.
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