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).