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

Abstract

Ag administered i.v. to mice along with specific IgE or IgG2a induces higher Ab- and CD4+ T cell responses than Ag administered alone. The IgE effect is completely dependent on the low-affinity receptor for IgE, CD23, whereas the IgG2a effect depends on activating FcγRs. In vitro studies suggest that IgE/Ag is presented more efficiently than Ag alone to CD4+ T cells by CD23+ B cells and that IgG2a/Ag is presented by FcγR+ dendritic cells (DCs). In this study, we investigate in vivo the early events leading to IgE- and IgG2a-mediated enhancement of immune responses. OVA administered i.v. in PBS in combination with specific IgE binds circulating B cells after 5 min and is found in B cell follicles bound to follicular B cells (CD23high) after 30 min. This novel B cell-dependent route of entry is specific for IgE because IgG2a-Ag complexes were trapped in the marginal zone. OVA-specific CD4+ T cells were found at the T-B border in the T cell zones 12 h after immunization both with IgE/OVA or IgG2a/OVA and proliferated vigorously after 3 days. The findings suggest that IgE- and IgG2a-immune complexes are efficient stimulators of early CD4+ T cell responses and that Ag bound to IgE has a specific route for transportation into follicles.

CD23-Dependent Transcytosis of IgE and Immune Complex across the Polarized Human Respiratory Epithelial Cells

“…6). This is, however, not surprising given the fact that CD23 has been described previously as mediating endocytosis of IC in B cells (28,55,56). However, several issues should be noticed.…”

Circulating specific antibodies enhance systemic cross‐priming by delivery of complexed antigen to dendritic cells in vivo

“…This is in line with recent work that demonstrated that i.v. injected IgG2a-antigen immune complexes reached the marginal zone of the spleen leading to recruitment of antigen-specific CD4 + T cell [21]. Previous work has indicated that intravenously injected preformed complexes, composed of IgG2a anti-TNP and OVA-TNP, efficiently induce CD4 + T-cell responses [9].…”

CD23b Isoform Expression in Human Schistosomiasis Identifies a Novel Subset of Activated B Cells

“…ϩ B cells play a role in the transportation of immune complexes from the blood to the follicular regions of the spleen (23). CXCR5 has a role in directing B cells to the lymphoid follicles, germinal centers (GC), and Peyer's patches (1).…”

“…The CD23b internal nucleotide sequence differs from that of CD23a, and there is no known role for CD23b in human B cells. As mentioned above, recent results suggest an important function for CD23 ϩ B cells in immune complex transport to the follicles in mice (23). In schistosomiasis, antigen capture and transport to the follicles via CXCR5 are likely highly relevant processes in the context of a chronic intravascular infection.…”

“…IgE bound to CD23 by B cells is thought to augment antigen presentation of captured antigens to T cells, but other roles, such as the transportation of immune complexes to splenic follicles, have been demonstrated in mice (23). However, although CD23b is inducible, the function of this isoform in human B cells is unknown.…”