The mTORC1/4E-BP/eIF4E Axis Promotes Antibody Class Switching in B Lymphocytes

Area of Science:

• Immunology
• Molecular Biology
• Cell Biology

Background:

• B cells differentiate into antibody-secreting plasma cells during adaptive immunity.
• Antibody (Ab) class switching produces Abs with diverse effector functions.
• Mammalian/mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) signaling is crucial for B cell class switching, but downstream mechanisms are unclear.

Purpose of the Study:

• To investigate the role of mTORC1 downstream substrates in B cell antibody class switching.
• To elucidate the mechanism by which mTORC1 regulates this process.

Main Methods:

• Used an in vitro murine B cell model.
• Inhibited mTORC1 with rapamycin after B cell division commitment.
• Investigated mTORC1 substrates and their impact on translation and protein expression.

Main Results:

• Disrupting the eIF4E-binding protein/eIF4E axis impaired B cell class switching.
• Reduced cap-dependent translation specifically affected activation-induced cytidine deaminase (Aicda) protein expression, not mRNA levels.
• Impaired Aicda protein expression decreased Ab class switching independently of proliferation.

Conclusions:

• Uncovered a novel role for the mTORC1 pathway and the eIF4E-binding protein/eIF4E axis in regulating Aicda protein expression.
• Demonstrated that cap-dependent translation controls key steps in mouse B cell differentiation and Ab class switching.