IgE-mediated enhancement of CD4+ T cell responses requires antigen presentation by CD8α− conventional dendritic cells

Abstract

IgE, forming an immune complex with small proteins, can enhance the specific antibody and CD4+ T cell responses in vivo. The effects require the presence of CD23 (Fcε-receptor II)+ B cells, which capture IgE-complexed antigens (Ag) in the circulation and transport them to splenic B cell follicles. In addition, also CD11c+ cells, which do not express CD23, are required for IgE-mediated enhancement of T cell responses. This suggests that some type of dendritic cell obtains IgE-Ag complexes from B cells and presents antigenic peptides to T cells. To elucidate the nature of this dendritic cell, mice were immunized with ovalbumin (OVA)-specific IgE and OVA, and different populations of CD11c+ cells, obtained from the spleens four hours after immunization, were tested for their ability to present OVA. CD8α− conventional dendritic cells (cDCs) were much more efficient in inducing specific CD4+ T cell proliferation ex vivo than were CD8α+ cDCs or plasmacytoid dendritic cells. Thus, IgE-Ag complexes administered intravenously are rapidly transported to the spleen by recirculating B cells where they are delivered to CD8α− cDCs which induce proliferation of CD4+ T cells.

CD23 provides a noninflammatory pathway for IgE-allergen complexes

“…Therefore we and others believe that CD23-expressing B cells likely act as carriers of IgE-immune complexes, which regulate IgE-dependent T-cell activation. 18,19,21 On the other hand, CD23 could also be understood as a decoy receptor for IgE-immune complexes, taking IgE away from the serum and from allergic effector cells. The outcome would still be that CD23 counteracts the allergic pathway to prevent sensitization.…”

“…[10][11][12][13][14][15][16][17] Furthermore, it has been shown that CD23 facilitates induction of antibody and T-cell responses. [18][19][20][21][22] IgE binding to its 2 primary receptors, FcεRI and CD23, is uniquely regulated by dynamic IgE structure-receptor relationships, whereas direct interaction between the 2 receptors through IgE molecules is prohibited by reciprocal allosteric inhibition. [23][24][25][26][27] This cross-inhibition is thought to be regulated by conformational plasticity of the IgE antibody, which can adopt 2 conformational states.…”

Impaired memory B‐cell development and antibody maturation with a skewing toward IgE in patients with STAT3 hyper‐IgE syndrome

“…was previously shown in the context of allergen-specific IgE. 31,32 However, given the fact that much of the IgE in STAT3-HIES patients does not appear to be allergen-specific, 17 HIES patient B cells did not produce more IgE than control B cells in these conditions, and it is interesting to note that the difference in antibody production between STAT3-HIES and controls in response to CD40L + IL-4 + IL-21 was smaller for IgE than for most other isotypes. This indicates that CSR to IgE is less severely impaired than CSR to most other isotypes.…”

A novel recycling mechanism of native IgE-antigen complexes in human B cells facilitates transfer of antigen to dendritic cells for antigen presentation

“…In a mouse model, a similar interaction of B cells and DCs has already been proposed. 40 To better understand the interactions of B cells and dendritic cells in humans, further studies are required, especially on the importance of DC subsets and on the B cell-derived signals that are inducers of costimulators. Furthermore, the uptake of IgE-ICs by DCs may not always be mediated by CD23 but also by FcεRI, which has been shown to be expressed in certain types of DCs.…”