Restoration of the Antibody Response to IgE/Antigen Complexes in CD23-Deficient Mice by CD23+ Spleen or Bone Marrow Cells

Abstract

Mice immunized with IgE/Ag complexes produce significantly more Ag-specific Abs than mice immunized with Ag alone. The enhancement is mediated via the low-affinity receptor for IgE (FcεRII or CD23), as shown by its complete absence in mice pretreated with mAbs specific for CD23 and in CD23-deficient mice. Because the constitutive expression of murine CD23 is limited to B cells and follicular dendritic cells (FDCs), one of these cell types is likely to be involved. One of the suggested modes of action of IgE/CD23 is to increase the ability of B cells to present Ag to T cells, as demonstrated to take place in vitro. Another possibility is that FDCs capture the IgE/Ag complexes and present these directly to B cells. The purpose of the present study was to determine whether CD23+ B cells or FDCs are responsible for the IgE/CD23-mediated enhancement of specific Ab responses in vivo. We show that the enhancement is completely restored in irradiated CD23-deficient mice reconstituted with CD23+ spleen or bone marrow cells. In these mice, the B cells are CD23+ and the FDCs are presumably CD23− because the FDCs are radiation resistant and are reported not to be replaced by donor cells after this type of cell transfer. In contrast, enhancement was not restored in irradiated wild-type mice reconstituted with CD23− cells. These results indicate that CD23+ B cells, and not FDCs, are the cells that capture IgE/Ag complexes and induce enhancement of Ab responses in vivo.

A Novel B Cell-Mediated Transport of IgE-Immune Complexes to the Follicle of the Spleen

“…9 and 19) as well as the ability to enhance Ab responses (9,19) are similar after immunization with IgE-and IgG2a-complexed Ag; the two Ab classes clearly use different mechanisms to achieve these effects. As described previously, IgE is dependent on CD23 expressed on B cells (18,19) and IgG2a requires activating Fc␥Rs expressed on a bone marrow-derived cell other than the B cell (which lacks activating Fc␥Rs) (7)(8)(9). Another difference, first described herein, is that IgG2a-Ag complexes are not transported as rapidly into the follicles as IgE-Ag complexes (Fig.…”

“…The only murine hematopoietic cells expressing CD23 are B cells and FDCs (20 -22). Since CD23 expression on B cells, but not on FDCs, is required for IgE-mediated enhancement (18,19), a mechanism involving transfer of IgE/Ag from FO B cells to FDCs, as shown to take place with IgM-and IgG-immune complexes (37,43) mechanism is CD23 dependent. Especially when using EBV-transformed B cell lines, which should be free of contaminating cell types, contribution of DCs to the T cell stimulation/Ag presentation is excluded (26 -28).…”

“…Studies in chimeric mice showed that CD23 had to be expressed on bone marrow-derived cells (i.e., B cells), but not on FDCs, in order for IgE to enhance Ab responses (18) and isolated CD23 ϩ B cells, transferred to CD23 Ϫ/Ϫ mice, rescued the ability of IgE to enhance Ab and T cell responses in these animals (19). It has been shown in vitro that CD23 ϩ human and murine B cells can capture IgE/Ag via CD23, endocytose and present Ag to specific T cells (25)(26)(27)(28)(29), and one hypothesis is that this mechanism explains IgE-mediated enhancement.…”

IgE Enhances Antibody and T Cell Responses In Vivo via CD23+ B Cells

“…First, IgE-Ag complexes may be captured by CD23 expressed on FDC and presented efficiently to B cells as immune complex-coated bodies, iccosomes. However, this is unlikely because chimeric mice, with CD23 ϩ FDC and CD23 Ϫ bone marrow (BM)-derived cells, are unresponsive to IgE-Ag complexes whereas mice with CD23 Ϫ FDC and CD23 ϩ BM-derived cells do respond (32). Because FDC and B cells are the only cell types proven to express the murine CD23a isoform in vivo (21,22), the lack of a role for FDC implies that the B cells are the effector cells.…”

Regulation of IgE Production Requires Oligomerization of CD23

“…Work done in CD23-deficient animals showed that the absence of CD23 resulted in no enhancement of Ag-specific IgG when these mice were injected with IgE anti-hapten/hapten-Ag complexes (45). More recently, Heyman et al (46) published that it is the CD23 on B cells that is responsible for the enhancement of IgE-mediated Ag presentation. Interestingly, mice treated with RAS1 produce less Ag-specific IgG1 than control animals.…”