Abstract
B cell differentiation and memory are controlled by the transmembrane activator and CAML interactor (TACI), a receptor encoded by TNFRSF13B. TNFRSF13B mutations are frequently found in common variable immunodeficiency (CVID) and in IgA -deficiency; yet, ~98% of those with mutant TNFRSF13B are healthy. Indeed, TNFRSF13B is among the 5% most polymorphic genes in man. Other mammals evidence polymorphism at comparable loci. We hypothesize that TNFRSF13B diversity might promote rather than detract from well-being by controlling key elements of innate immunity. We shall discuss how extraordinary diversity of TNFRSF13B could have evolved and persisted across diverse species of mammals by controlling innate and adaptive B cell responses in apparently paradoxical ways.
Highlights
B cell responses are often characterized as T cell-independent or T cell-dependent that differ on how T cells are engaged
The secreted form of IgA is a complex comprised of an IgA dimer linked by the joining (J) chain and a secretory component, a fragment of the polymeric Ig receptor (PIgR)
There is no evidence in support of TNFRSF13B direct influence on IgA glycosylation, by controlling IgA secretion TNFRSF13B is likely to impact more on the nonspecific IgA functions than on the functions of IgA that depend on high affinity interactions between mutated V regions and their targets
Summary
B cell responses are often characterized as T cell-independent or T cell-dependent that differ on how T cells are engaged. The differential impact of TNFRSF13B on T cell-independent and T-cell-dependent responses may reflect differences in how Blimp-1 is induced. The secreted form of IgA is a complex comprised of an IgA dimer linked by the joining (J) chain and a secretory component, a fragment of the polymeric Ig receptor (PIgR). IgA complexed with J chain and the secretory component is heavily glycosylated and glycosylation is necessary for many of non-specific, variable region-independent IgA functions [49]. There is no evidence in support of TNFRSF13B direct influence on IgA glycosylation, by controlling IgA secretion TNFRSF13B is likely to impact more on the nonspecific IgA functions than on the functions of IgA that depend on high affinity interactions between mutated V regions and their targets
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