TNFRSF13B Diversification Fueled by B Cell Responses to Environmental Challenges—A Hypothesis

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Abstract
B cell differentiation and memory are controlled by the transmembrane activator and CAML interactor (TACI), a receptor encoded byTNFRSF13B.TNFRSF13Bmutations are frequently found in common variable immunodeficiency (CVID) and in IgA -deficiency; yet, ~98% of those with mutantTNFRSF13Bare healthy. Indeed,TNFRSF13Bis among the 5% most polymorphic genes in man. Other mammals evidence polymorphism at comparable loci. We hypothesize thatTNFRSF13Bdiversity might promote rather than detract from well-being by controlling key elements of innate immunity. We shall discuss how extraordinary diversity ofTNFRSF13Bcould have evolved and persisted across diverse species of mammals by controlling innate and adaptive B cell responses in apparently paradoxical ways.
Funding Information
  • NIH Office of the Director (AI122369, AI51588, GM140359)
  • Medical School, University of Michigan (CASE-283529 UM-MTRAC, MICHR Accelerating Synergy Award)

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