Allospecific Memory B Cell Responses Are Dependent on Autophagy.

Area of Science:

• Immunology
• Cell Biology
• Transplantation Science

Background:

• Long-lived, donor-reactive memory B cells (Bmems) produce alloantibodies contributing to transplant injury.
• Autophagy is essential for Bmem survival in various contexts, but its role in alloreactive Bmems is unclear.

Purpose of the Study:

• To investigate the role of autophagy in the survival and function of alloreactive Bmems.
• To determine if targeting autophagy can be a strategy to prevent transplant injury.

Main Methods:

• Utilized a reporter mouse model to identify and track alloreactive Bmems.
• Generated mice with conditional deficiency in the autophagy gene ATG7 in B cells.
• Assessed B cell autophagy, alloantibody production, and Bmem frequencies.
• Used pharmacological autophagy inhibition.

Main Results:

• Alloreactive Bmems exhibited higher levels of autophagosomes compared to naive B cells.
• Conditional deficiency of ATG7 in B cells abolished B cell autophagy and inhibited secondary alloantibody responses.
• Reduced frequencies of alloreactive Bmems were observed in ATG7-deficient mice.
• Pharmacological inhibition of autophagy mimicked these effects.

Conclusions:

• Autophagy is critical for the survival and function of alloreactive Bmems.
• Targeting autophagy presents a potential therapeutic strategy for eliminating donor-reactive Bmems and mitigating transplant injury.