IgE repertoire and immunological memory: compartmental regulation and antibody function

Abstract

It is now generally recognised that bone marrow is the survival niche for antigen-specific plasma cells with long-lived immunological memory. These cells release antibodies into the circulation, needed to prime effector cells in the secondary immune response. These antibodies participate in the surveillance for antigen and afford immune defence against pathogens and toxins previously encountered in the primary immune response. IgE antibodies function together with their effector cells, mast cells, to exert "immediate hypersensitivity" in mucosal tissues at the front line of immune defence. The constant supply of IgE antibodies from bone marrow plasma cells allows the rapid "recall response" by mast cells upon re-exposure to antigen even after periods of antigen absence. The speed and sensitivity of the IgE recall response and potency of the effector cell functions are advantageous in the early detection and elimination of pathogens and toxins at the sites of attack. Local antigen provocation also stimulates de novo synthesis of IgE or its precursors of other isotypes that undergo IgE switching in the mucosa. Such process, however, introduces a delay before mast cells can be sensitized and resume activity; this is terminated shortly after the antigen is eliminated. Recent results from adaptive immune receptor repertoire sequencing (AIRR-Seq) of immunoglobulin genes suggest that the mucosal IgE⁺ plasmablasts, which have undergone affinity maturation in the course of their evolution in vivo, are a source of long-lived IgE⁺ plasma cells in the bone marrow that are already fully functional.