AUTHOR=Cascalho Marilia , Platt Jeffrey L. 

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

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.634544

DOI=10.3389/fimmu.2021.634544

ISSN=1664-3224

ABSTRACT=<p>B cell differentiation and memory are controlled by the transmembrane activator and CAML interactor (TACI), a receptor encoded by <italic>TNFRSF13B</italic>. <italic>TNFRSF13B</italic> mutations are frequently found in common variable immunodeficiency (CVID) and in IgA -deficiency; yet, ~98% of those with mutant <italic>TNFRSF13B</italic> are healthy. Indeed, <italic>TNFRSF13B</italic> is among the 5% most polymorphic genes in man. Other mammals evidence polymorphism at comparable loci. We hypothesize that <italic>TNFRSF13B</italic> diversity might promote rather than detract from well-being by controlling key elements of innate immunity. We shall discuss how extraordinary diversity of <italic>TNFRSF13B</italic> could have evolved and persisted across diverse species of mammals by controlling innate and adaptive B cell responses in apparently paradoxical ways.</p>