<i>In vivo</i> enhancement of the specific antibody response via the low‐affinity receptor for IgE

Heyman, Birgitta; Liu, Tianmin; Gustavsson, Susanne

doi:10.1002/eji.1830230754

Cited by 97 publications

(97 citation statements)

References 26 publications

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“…First, not only MZ B cells (50), but also FO B cells, are able to present Ag. Second, although the majority of the Ag-presenting B cells would be unspecific (because they capture Ag via CD23 and not via the B cell receptor), the ensuing enhanced Ab response is strictly Ag specific (14,15), demonstrating that cognate interactions between CD4 ϩ T cells and B cells are required also in this situation. The biological role of IgE-mediated enhancement of immune responses is enigmatic.…”

Section: Discussionmentioning

confidence: 99%

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

Hjelm

Karlsson

Heyman

2008

The Journal of Immunology

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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.

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Section: Discussionmentioning

confidence: 99%

“…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).…”

mentioning

confidence: 99%

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

Hjelm

Karlsson

Heyman

2008

The Journal of Immunology

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“…CD23 could enhance IgE antigen complex presentation 100-fold more than either unfocused or IgG bound antigen in animal studies. [25][26][27] The proposed roles for CD23 in antigen presentation include the binding of antigen-IgE-antibody complexes, internalization of the complexes, transport to compartments of the endosomal network containing proteolytic enzymes, interaction with major histocompatibility complex (MHC) class II antigens and interaction with CD21 at the points of contact on the Band T-cell surfaces. 28,29 An integrated CD23 is believed to be important for the IgE-mediated antigen presentation.…”

Section: Discussionmentioning

confidence: 99%

Polymorphism R62W results in resistance of CD23 to enzymatic cleavage in cultured cells

McFall

2007

Genes Immun

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A nonsynonymous single nucleotide polymorphism (SNP) of the low-affinity IgE receptor (FceRII/CD23) gene resulting in an arginine to tryptophan exchange at amino-acid position 62 (R62W) has been associated with enhanced T-cell responses to antigen in allergic subjects. To explore the mechanism, a CD23(a) cDNA was cloned into the plasmid pCMVScript-CD23a-C with a C allele (R62). The pCMVScript-CD23a-T with T (W62) was produced using a site-directed mutagenesis approach. The pCMVScript-CD23a-C only (CC), mixture of pCMVScript-CD23a-T and pCMVSCript-CD23a-C (CT) and pCMVScript-CD23a-T only (TT) plasmids were transfected in Cos-7 cells at equivalence in transfection efficiency. No soluble CD23 was released from TT transfectants whereas a higher level of soluble CD23 was detected in CC than in CT transfectants. Human leukocyte elastase (HLE), cathepsin G, the dust mite allergen Der p I and ADAM 33 (A disintegrin and metalloproteinase) were found to cleave membrane CD23 in CC but not in TT transfectants, implying the resistance of CD23 to enzymatic cleavage associated with T mutant. Addition of tunicamycin resulted in the resistance of CD23 to Der p I mediated cleavage in CC but no change in TT transfectants. These results indicate that R62W influences the stability of membrane CD23 molecules due to possibly diminished N-glycosylation.

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“…Previous studies of IgE-induced antibody responses have exclusively measured serum responses [4,5,18,21]. To investigate the single B-cell response after immunization with IgE and antigen, ELISPOT assays were performed in parallel to ELISA.…”

Section: Ige Up-regulates the Number Of Specific B Cells In Spleenmentioning

confidence: 99%

“…The most recently discovered member of the family of 'enhancing isotypes' is IgE. In 1993 it was shown that mice given TNP-specific IgE before immunization with BSA-TNP produced up to 100-fold more BSA-specific antibodies than mice given antigen alone [4]. The enhancement affected specific IgG1-, IgG2a-, IgM-as well as IgE production, was dependent on T cells, and induced immunological memory [5].…”

Section: Introductionmentioning

confidence: 99%

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

1997

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IgE antibodies have potent immunoregulatory effects in vivo, and mice immunized with IgE–antigen (IgE/Ag) complexes exhibit a several hundred‐fold higher humoral Ag‐specific response than mice immunized with non‐complexed Ag. In vitro studies indicate that this is a result of efficient endocytosis of the IgE/Ag complexes via the low‐affinity receptor for IgE (CD23) on B cells, leading to efficient antigen presentation to T cells. Previous studies of IgE‐induced Ab responses in vivo have only measured serum responses. The authors have now studied the up‐regulated response as the number of IgG‐, IgA‐, IgE‐ and IgM‐secreting single B cells in spleen, lymph nodes and bone marrow of mice immunized with IgE‐anti‐TNP + BSA‐TNP (2,4,6‐trinitrophenylated bovine serum albumin). IgE and Ag induced a greater than 500‐fold increase of specific IgG‐secreting spleen cells with the peak of the response 6 days after primary immunization. The response of other Ab isotypes and the response in other lymphoid organs was marginal. The rapid increase in the number of IgG‐secreting cells in the spleen suggests that IgE/Ag complexes induce a secondary type of antibody response without requirement for conventional priming.

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In vivo enhancement of the specific antibody response via the low‐affinity receptor for IgE

Cited by 97 publications

References 26 publications

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

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

Polymorphism R62W results in resistance of CD23 to enzymatic cleavage in cultured cells

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

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