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Humoral immunity is seeded by affinity between the B cell receptor (BCR) and cognate antigen. While the BCR is a chimeric display of diverse antigen engagement solutions, we discuss its functional activity as an ‘innate-like’ immune receptor, wherein genetically hardwired antigen complementarity can serve as reproducible templates for pathway-amplifying otherwise immunologically recessive antibody responses. We propose that the capacity for germline reactivity to new antigen emerged as a set of evolutionary spandrels or coupled traits, which can now be exploited by rational vaccine design to focus humoral immunity upon conventionally immune-subdominant antibody targets. Accordingly, we suggest that evolutionary spandrels account for the necessary but unanticipated antigen reactivity of the germline antibody repertoire.

Public Immunity: Evolutionary Spandrels for Pathway-Amplifying Protective Antibodies