BAFFR controls early memory B cell responses but is dispensable for germinal center function

Area of Science:

• Immunology
• Cell Biology

Background:

• The TNF superfamily ligand BAFF is essential for naive B cell survival via BAFFR signaling.
• Activated B cells express BAFFR, but its role in germinal center (GC) and memory B cells (MBCs) is unclear.

Purpose of the Study:

• To investigate the function of BAFFR in GC B cells and MBCs.
• To elucidate the specific role of BAFF/BAFFR signaling in different B cell populations.

Main Methods:

• Investigated B cell-intrinsic BAFFR function in GC B cells and MBCs.
• Analyzed the impact of BAFF/BAFFR signaling on GC-independent MBC generation.
• Examined the effect of amplified BAFFR signaling on GC and MBC responses.

Main Results:

• B cell-intrinsic BAFFR is not critical for GC B cell survival or function, nor for generating somatically mutated MBCs.
• BAFF/BAFFR signaling is essential for generating unmutated, GC-independent MBCs from early activated B cell blasts.
• Amplified BAFFR signaling expanded GC-independent MBCs without affecting GCs or GC-derived MBCs.
• Both GC-independent and GC-derived MBCs require BAFF/BAFFR signaling for optimal long-term survival.

Conclusions:

• BAFF/BAFFR signaling specifically regulates the formation of GC-independent MBCs.
• This pathway is indispensable for the long-term survival of all memory B cell subsets.