IgA synthesis: a form of functional immune adaptation extending beyond gut

Re-thinking the functions of IgA+plasma cells

“…This is presumably mediated by a consequential skewing of the commensal microbial composition in the absence of IgA, thus affecting energy harvest from the diet and changes in the immunological and metabolic function of IEC. 90,91,93 The molecular features of malabsorption found in B cell-deficient mice were also found in IgA-deficient mice as well as humans with common variable immunodeficiency or HIV infection, suggesting that the homeostatic and metabolic mechanisms exerted by IgA in the human gut may be similar to those observed in mice. 90 These alterations have been shown to lead to an increased risk in the development of chronic inflammatory disorders and autoimmune disease, 93,94 thus underscoring the critical role of IgA for the regulation of intestinal and systemic immune system homeostasis.…”

Seasonal restructuring of the ground squirrel gut microbiota over the annual hibernation cycle

“…It is likely that seasonal reorganization of the microbiota is a major driver of these immune alterations, because the immune system is the primary sensor of gut microbes and their metabolites (30,63). Immune changes are often associated with altered host-microbe signaling (30,36,53,61) and may function to maintain a mutually beneficial, tolerant state (19,46). The elevation in intestinal secretory IgA (sIgA) expression during hibernation (35) provides particularly strong evidence for a seasonal shift in host-gut microbe signaling.…”

“…The elevation in intestinal secretory IgA (sIgA) expression during hibernation (35) provides particularly strong evidence for a seasonal shift in host-gut microbe signaling. Gut microbiota can stimulate sIgA production (61,62), and there is growing evidence that in addition to preventing bacterial adherence to epithelial cells, sIgA plays a key regulatory role in maintaining the complex, mutualistic interactions between the microbiota, the epithelium, and the immune system (53,61). Further, hibernation is accompanied by increased levels of mucosal IL-10, a potent anti-inflammatory cytokine that promotes immune tolerance of the microbiota (35,46).…”

Naturally secreted immunoglobulins limit B1 and MZ B-cell numbers through a microbiota-independent mechanism

“…For instance, IgM play a role in tissue integrity through clearance of apoptotic cells, misfolded proteins, and inhibition of proinflammatory signals; polyspecific IgGs (pIgGs) purified from plasma of healthy donors (IVIg) can be used for their antiinflammatory properties to treat patients suffering from autoimmune diseases; 1,2 and IgA maintain gut mucosa homeostasis through the control of commensal bacteria, thereby preventing chronic inflammation. 3 Igs of different classes exert some homeostatic functions independently of their antigenic specificity through their constant regions or Fc portions that bind activating or inhibitory Fc receptors (FcRs). 4,5 The homeostatic functions of Igs can also involve their antigen (Ag) recognition domains; maintenance of mucosal homeostasis requires somatic hypermutation (SHM) of the IgA variable regions, a process increasing their affinity for gut bacteria.…”