BAFF, APRIL and their receptors: structure, function and signaling

Area of Science:

• Immunology
• Molecular Biology
• Cell Biology

Background:

• The B-cell immune system relies on the signaling interactions of BAFF (B-cell activating factor) and APRIL (A Proliferation Inducing Ligand).
• Multiple splice isoforms exist for these ligands and their receptors, with varying conservation across species.
• Understanding these interactions is crucial for comprehending B-cell homeostasis and immune responses.

Purpose of the Study:

• To elucidate the immunological roles of BAFF, APRIL, and their receptors in the B-cell compartment.
• To characterize the specificity of receptor-ligand interactions within this subfamily.
• To investigate the incompletely understood molecular signaling events downstream of BAFF and APRIL receptor engagement.

Main Methods:

• Structural and mutational analyses were employed to determine receptor-ligand specificity.
• Investigation of downstream signaling pathways, including NF-kappaB activation and protein degradation.
• Analysis of B-cell survival mechanisms and activation events.

Main Results:

• BAFF-R exhibits high selectivity for BAFF, BCMA preferentially binds APRIL, and TACI interacts with both ligands.
• Downstream signaling involves upregulation of Bcl-2 family members via NF-kappaB activation.
• Mechanisms for B-cell survival include Bim protein degradation and PCKdelta localization control.

Conclusions:

• BAFF and APRIL signaling pathways are critical for B-cell function, particularly survival.
• Receptor-ligand specificity is well-defined, but downstream signaling events require further characterization.
• Future research should focus on non-canonical signaling pathways involved in B-cell activation and Ig class switching.