Early Expansion of Secondary B Cells after Primary Immunization with Antigen Complexed with IgE

101

IgE Abs, passively administered together with their specific Ag, can enhance the production of Abs recognizing this Ag by >100-fold. IgE-mediated feedback enhancement requires the low affinity receptor for IgE, CD23. One possible mechanism is that B cells take up IgE-Ag via CD23 and efficiently present Ag to Th cells, resulting in better Ab responses. To test whether IgE Abs have an effect on Th cells in vivo, mice were adoptively transferred with CD4+ T cells expressing a transgenic OVA-specific TCR, before immunization with IgE anti-TNP (2,4,6-trinitrophenyl) plus OVA-TNP or with OVA-TNP alone. IgE induced a 6- to 21-fold increase in the number of OVA-specific T cells. These cells acquired an activated phenotype and were visible in splenic T cell zones. The T cell response peaked 3 days after immunization and preceded the OVA-specific Ab response by a few days. Transfer of CD23+ B cells to CD23-deficient mice rescued their ability to respond to IgE-Ag. Interestingly, in this situation also CD23-negative B cells produce enhanced levels of OVA-specific Abs. The data are compatible with the Ag presentation model and suggest that B cells can take up Ag via “unspecific” receptors and activate naive T cells in vivo.

Section: Ige Enhances Antibody and T Cell Responsesmentioning

confidence: 99%

Section: Ige Enhances Antibody and T Cell Responsesmentioning

confidence: 99%

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

Getahun

Hjelm

Heyman

2005

101

“…The number of B cells secreting BSA-specific IgG was determined using an ELISPOT assay (26). Spleens were removed and cell suspensions were prepared in DMEM with 0.5% normal mouse serum.…”

Section: Elispot Assaymentioning

confidence: 99%

IgG2a-Mediated Enhancement of Antibody and T Cell Responses and Its Relation to Inhibitory and Activating Fcγ Receptors

Getahun

Dahlström

Wernersson

et al. 2004

A number of studies in experimental animal models point to an important role of FcγRs in autoimmunity and allergy. In this study, we investigate how the production of IgG, an early step in the chain of events leading to inflammation, is regulated by activating and inhibitory FcγRs. IgG Abs are known to feedback-enhance Ab responses to soluble Ags, and this effect requires activating FcγRs. To test proliferation of Th cells, mice were adoptively transferred with CD4+ T cells expressing a transgenic OVA-specific TCR before immunization with IgG2a anti-2,4,6-trinitrophenyl (TNP) plus OVA-TNP or with OVA-TNP alone. IgG2a induced a significant increase in OVA-specific T cell numbers, which preceded the OVA-specific Ab response and was dependent on the FcRγ chain. The role of the inhibitory FcγRIIB in Ab responses was studied in mice lacking this receptor. Although IgG2a enhanced primary Ab responses, development of germinal centers, and immunological memory in wild-type mice, enhancement was markedly stronger in FcγRIIB−/− mice. The presented data are compatible with the hypothesis that the mechanism behind IgG2a-mediated up-regulation of Ab responses involves increased Ag presentation to CD4+ T cells by FcγR+ APCs. Our observations also illustrate the intricate immunoregulatory role of IgG Abs. On the one hand, they enhance Ab responses via activating FcγRs, and on the other hand, they set an upper limit for the same Ab response via FcγRIIB.

“…The enhanced Ab response takes place in the absence of adjuvants and is constrained to antigenic determinants within the Ab-Ag complex (14,15). IgE administered with Ag enhances the production of specific primary IgG1, IgG2a, IgM, as well as IgE (15,17) and also induces a more efficient immunological memory than Ag alone (15). The IgG response peaks as early as 6 days after a primary immunization and remains high for several weeks (17).…”

mentioning

confidence: 99%

“…IgE administered with Ag enhances the production of specific primary IgG1, IgG2a, IgM, as well as IgE (15,17) and also induces a more efficient immunological memory than Ag alone (15). The IgG response peaks as early as 6 days after a primary immunization and remains high for several weeks (17). IgE-mediated enhancement is abrogated in mice lacking the lowaffinity receptor for IgE (Fc RII, CD23) or when CD23 is blocked by CD23-specific mAbs (14 -18), thus demonstrating the complete dependence on CD23.…”

mentioning

confidence: 99%

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

Hjelm

Karlsson

Heyman

2008

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.