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Characterization of Thymus-dependent and Thymus-independent Immunoglobulin Isotype Responses in Mice Using Enzyme-linked Immunosorbent Assay
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Shaping Polyclonal Responses via Antigen-Mediated Antibody Interference.

Le Yan1, Shenshen Wang2

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Summary
This summary is machine-generated.

Antibody interference shapes B cell responses by influencing clonal selection. Antagonism can boost rare, broadly neutralizing antibody clones but may reduce overall immune protection.

Keywords:
Biological SciencesImmunologyMathematical Biosciences

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Area of Science:

  • Immunology
  • Computational Biology
  • Systems Biology

Background:

  • Broadly neutralizing antibodies (bnAbs) are crucial for universal protection against mutating pathogens but are rare in natural infections.
  • Antibodies can interfere with B cell selection, but the impact on polyclonal responses remains unclear.

Purpose of the Study:

  • To develop a framework for understanding how antibody interference shapes B cell clonal composition and bnAb lineage fate.
  • To investigate the role of multi-epitope antigens in mediating antibody interference.

Main Methods:

  • Developed a theoretical framework analyzing antigen-mediated clonal interactions.
  • Modeled heterogeneous interference effects on B cell clones with varying intrinsic fitness.
  • Examined the impact of antagonism and synergy among clones targeting conserved and variable epitopes.

Main Results:

  • Heterogeneous interference allows collective persistence of B cell clones with different fitness levels.
  • Antagonism between high-fitness clones (variable epitopes) promotes low-fitness clones (conserved epitopes), potentially reducing repertoire potency.
  • Synergy towards low-fitness clones can mitigate the trade-off between clonal expansion and repertoire potency.

Conclusions:

  • Antigen-mediated antibody interference significantly impacts B cell clonal dynamics and repertoire quality.
  • Understanding clonal interactions, synergy, and antagonism provides principles for enhancing rare, protective B cell clones.
  • This work offers insights into the system-level effects of molecular interactions in immune responses.