Fostering of advanced mutualism with gut microbiota by Immunoglobulin A

Abstract

Immunoglobulin A (IgA), the most abundantly secreted antibody isotype in mammals, not only provides direct immune protection to neonates via maternal milk but also helps program the infant immune system by regulating the microbiota. IgA continues to maintain dynamic interactions with the gut microbiota throughout life and this influences immune system homeostasis as well as other physiological processes. The secretory IgA produced independently of T-cell selection are commonly referred to as natural or innate antibodies. Our studies have shown that innate-IgA, while effective at excluding microorganisms from the gut, does not promote mutualism with the microbiota in the same way as adaptive-IgA that is selected in T cell-dependent germinal center reactions. Adaptive-IgA fosters more advanced mutualism with the microbiota than innate-IgA by selecting and diversifying beneficial microbial communities. In this review, we suggest that the diversified microbiota resulting from adaptive-IgA pressure was pivotal in promoting ecological adaptability and speciation potential of mammals.

T Follicular Helper Cells Promote a Beneficial Gut Ecosystem for Host Metabolic Homeostasis by Sensing Microbiota-Derived Extracellular ATP

“…Bacterial coating by IgA restricts bacterial access to the epithelium and can promote the survival of specific bacteria that affect the intestinal as well as general metabolism (Mantis et al., 2011). Moreover, the diversified microbiota resulting from T-dependent secretory IgA pressure has been suggested to play a pivotal role in promoting the ecological adaptability and speciation potential of mammals (Sutherland et al., 2016). …”

Germinal Center B Cell Dynamics

“…Whereas protein model antigens adsorbed in alum usually induce short-lived GCs that collapse within the first month after immunization, certain synthetic vaccines, viral infections or the gut microbiota can induce GCs that remain active for much longer periods, if not indefinitely (Adachi et al, 2015; Bachmann et al, 1996; Kasturi et al, 2011; Sutherland et al, 2016). Prolonged GC reactions may allow B cells to reach a higher degree of affinity maturation (Klein et al, 2013; Pappas et al, 2014) and may represent a means to cope with the antigenic drift associated with chronic viral infection (Bonsignori et al, 2016; Liao et al, 2013).…”

Homeostatic Immunity and the Microbiota

“…IgA (maternal IgA, innate and adaptive IgA) is the most abundant secreted isotype in mammals and play a fundamental role in shaping early interactions with the microbiota as well as in maintaining microbiota diversity and compartmentalization through life (Kawamoto et al, 2014; Sutherland et al, 2016). Secretory IgA can be produced in both T independent (referred to as innate) and T cell dependent manners (referred to as adaptive).…”

“…Secretory IgA can be produced in both T independent (referred to as innate) and T cell dependent manners (referred to as adaptive). While innate IgA can exclude microorganisms from the gut, those are not as potent as adaptive IgA in shaping mutualistic relationship with the microbiota (Kawamoto et al, 2014; Sutherland et al, 2016). …”