Public Immunity: Evolutionary Spandrels for Pathway-Amplifying Protective Antibodies

Area of Science:

• Immunology
• Molecular Biology
• Evolutionary Biology

Background:

• Humoral immunity relies on B cell receptor (BCR) affinity for antigen recognition.
• BCRs exhibit diverse antigen-binding capabilities, functioning akin to innate immune receptors.
• Genetically determined antigen complementarity in BCRs can amplify immune responses.

Purpose of the Study:

• To explore the functional activity of the BCR as an 'innate-like' immune receptor.
• To propose that germline reactivity to new antigens arose as evolutionary spandrels.
• To suggest exploiting these evolutionary traits for rational vaccine design against subdominant targets.

Main Methods:

• Conceptual analysis of BCR function and germline reactivity.
• Review of evolutionary principles (spandrels) applied to immune system development.
• Discussion of implications for vaccine development strategies.

Main Results:

• BCRs possess innate-like properties, enabling amplification of antibody responses through genetically hardwired complementarity.
• The capacity for germline reactivity to novel antigens is proposed to be an evolutionary byproduct (spandrels).
• These evolutionary spandrels represent a mechanism for generating necessary, albeit unanticipated, antigen reactivity in the germline repertoire.

Conclusions:

• The innate-like function of BCRs provides a template for amplifying immune responses to otherwise recessive antigens.
• Evolutionary spandrels explain the germline repertoire's reactivity to new antigens.
• Rational vaccine design can harness these evolutionary traits to focus humoral immunity on conventionally subdominant epitopes.