Intracellular Trafficking of CD23: Differential Regulation in Humans and Mice by Both Extracellular and Intracellular Exons

Abstract

In mouse models of food allergy, we recently characterized a new CD23b-derived splice form lacking extracellular exon 5, bΔ5, which undergoes constitutive internalization and mediates the transepithelial transport of free IgE, whereas classical CD23b is more efficient in transporting IgE/allergen complexes. These data suggested that regulation of endocytosis plays a central role in CD23 functions and drove us to systematically compare the intracellular trafficking properties of human and murine CD23 splice forms. We found that CD23 species show similar endocytic behaviors in both species; CD23a undergoes constitutive clathrin-dependent internalization, whereas CD23b is stable at the plasma membrane. However, the mechanisms controlling these similar behaviors appeared to be different. In mice, a positive internalization signal was localized in the cytoplasmic region shared by all CD23 splice forms. This positive signal was negatively regulated by the intracellular CD23b-specific exon. In addition, the fact that alternative splice forms lacking exons of the extracellular region (5, 6, 7, and/or 8) were all constitutively internalized suggested that endocytosis of murine CD23 is regulated by a process similar to the outside-in signaling of integrins. In humans, the internalization signal was mapped in the CD23a-specific intracellular exon. Interestingly, this signal also behaved as a basolateral targeting signal in polarized Madin-Darby canine kidney cells. The latter result and the fact that human intestinal cell lines were found to coexpress both CD23a and CD23b provide a molecular explanation for the initial observations that CD23 was found at the basolateral membrane of intestinal epithelial cells from allergic patients.

CD23 Sheddase A Disintegrin and Metalloproteinase 10 (ADAM10) Is Also Required for CD23 Sorting into B Cell-derived Exosomes

“…This data are summarized in Table 1. CD23 co-localization with EEA1 and Rab11 indicates endosomal trafficking and is in agreement with previous work that showed that CD23 traffics through the endosomal pathway (31,32).…”

“…To further investigate this phenomena, we first sought to confirm studies (31,32) that showed that anti-CD23 cause ligand internalization. mCD23 ϩ -CHO cells were labeled with FITC-anti-CD23 (FITC-B3B4), which is an antilectin mAb, transferred to 37°C and internalization was followed (Fig.…”

Maternal Transmission of Resistance to Development of Allergic Airway Disease

“…Because offspring of naive mothers were devoid of OVA-specific IgE and the fact that no mechanism to facilitate transplacental transport of IgE is thought to exist in mice or humans, the presence of OVA-specific IgE in serum of nursing offspring suggested that acquisition of maternal IgE from immune mothers was a result of intestinal absorption from breast milk. The low-affinity IgE receptor, CD23, is expressed by intestinal epithelial cells and specific isoforms are responsible for absorption of IgE or IgE immune complexes from the intestinal lumen (74,75). The potential for repercussions from maternally transmitted IgE or IgE immune complexes from breast milk are likely significant in offspring.…”

The high-affinity IgE receptor (FcεRI): a critical regulator of airway smooth muscle cells?

“…CD23 and a novel CD23b-derived alternative splice form CD23b⌬5 in rapid transepithelial transport of IgE/allergen complexes and subsequent delivery of intact antigen to mast cells in the subepithelial compartment (77,78).…”