Antibody-mediated feedback modulates interclonal competition in the germinal center

Area of Science:

• Immunology
• Molecular Biology

Background:

• Prior antibody responses regulate B cell activation and germinal center (GC) entry.
• The influence of antibodies from contemporaneous immune responses on GC outcomes is not well understood.

Purpose of the Study:

• To investigate how antibodies produced during an ongoing immune response affect contemporaneous germinal centers.
• To elucidate the role of antibody feedback in shaping B cell competition and epitope specificity within GCs.

Main Methods:

• Development of a novel mouse model allowing conditional ablation of plasma cells (PCs) and their antibodies.
• Utilizing tamoxifen-inducible Cre-lox system to target Prdm1 locus for PC-specific diphtheria toxin receptor expression.
• Analysis of B cell competition and epitope specificity in germinal centers following antigen challenge.

Main Results:

• Antibody-mediated feedback was not essential for B cell affinity maturation.
• Antibody feedback modulated competition between B cells recognizing different epitopes.
• A reduction in clones recognizing the same epitopes as soluble antibodies from PCs was observed.

Conclusions:

• Antibodies produced during an ongoing immune response can shape epitope specificity in germinal centers.
• This antibody feedback mechanism influences immunodominance hierarchies.
• Findings have implications for designing vaccines that direct immune responses toward specific epitopes on complex antigens.