5. CD23 in the activation of B cells and monocytes
Many functional investigations on CD23 have demonstrated a mechanism triggered by CD23 cross-linking via IgE immune complexes. It has been known for quite some time that CD23 cross-linking leads to internalization. The mechanism of uptake is different for the two CD23 isoforms CD23a and CD23b (31). The differential expression of CD23a and b in B cells and monocyte-related cells, respectively has led to several interesting comparative studies showing differential signalling. Specifically, signalling via Fyn and Syk and Akt pathways resulting in IFN-γ production was only reported for CD23 cross-linking in B cells whereas cells of the monocytic lineage have been described to signal via IκB and produce inflammatory chemokines and cytokines such as TNF, IL-1β, IL-1ra, IL-10, IL-8, MCP-1, and MIP-1α (64–68). A recent paper has shown that CD23 as well can negatively regulate BCR activation on B cells by promoting B cell contraction. This provides an explanation for down-regulation of CD23 on memory B cells that mount a higher response of memory B cells to antigenic stimulation (69).
In addition to the differential signalling, the processing of IgE and IgE-immune complexes also depends on the cell type. In monocyte-derived cells or in dendritic cells only expressing CD23b, IgE and allergen are targeted to a degradative pathway after CD23 cross-linking. In contrast, human primary B cells expressing CD23a in addition to CD23b, protect IgE and allergen from degradation and recycle IgE-immune complexes via CD23 allowing transfer to other immune cells (70, 71) (Fig. 2). These findings are consistent with studies in mice showing that circulating murine B cells transport IgE immune complexes to the spleen (72–74).
Those findings in B cells fit well to results showing that CD23a expressing human intestinal epithelial cells (75,76) as well as mouse intestinal epithelial cells can shuttle IgE and IgE-immune complexes through the epithelial layer by transcytosis (77). Like in human B cells, food allergens were also shown to be protected from degradation during epithelial transcytosis (78). Interestingly, intestinal epithelial cells (IEC) were also shown to release CCL20 in response to CD23 cross-linking, suggesting that CD23 may act as critical receptor in initiating an allergic response by the release of chemokines capable of recruiting cells of the innate and adaptive immune system (79). Furthermore, CD23-dependent transcytosis of IgE immune complexes was described for human airway epithelial cells (AEC), however in contrast to B cells and IEC, CD23b was the reported isoform involved in AEC (76).