Diversification Fueled by B Cell Responses to Environmental Challenges-A Hypothesis.

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