Fig. 2.

B cell activation. In response to Th2-derived IL-4 and IL-13, naïve B cells migrate to B cell follicles for proliferation and formation of germinal centers. In incompletely organized germinal centers, as found in the Th2-centric response, naïve B cells undergo somatic hypermutation and class-switch recombination as part of direct switching to IgE⁺ B cells. In mature germinal centers, naïve B cells undergo indirect switching, passing through an intermediate IgG₄⁺ B cell phase before transforming into IgE⁺ B cells. In either case, IgE⁺ B cells can then leave the germinal center, becoming either memory B cells or long-lived plasma cells. Memory B cells are dividing cells that produce minimal IgE but allow the prompt production of specific IgE-secreting plasma cells following a secondary allergen exposure in the absence of cytokines. It is not well established where IgE memory resides, and this remains a topic under active investigation within the field. Plasma cells do not divide, but produce far more specific IgE. Figure

adapted from Akdis M and Akdis CA. Nat Immunol 2012;13(4):312–314 and Davies JM, et al. J Allergy Clin Immunol 2013;131(4):972–976. IgE immunoglobulin E, IgG immunglobulin G, IgM immunoglobulin M, IL interleukin, ILC innate lymphoid cell, MHCII major histocompatibility complex class II, TCR T cell antigen receptor, Th2 T helper 2