A novel B cell-mediated transport of IgE-immune complexes to the follicle of the spleen.
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 FcgammaRs. 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 FcgammaR(+) 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 (CD23(high)) 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.
Hjelm
Fredrik
F
Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
Karlsson
Mikael C I
MC
Heyman
Birgitta
B
D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000936:Antigen-Antibody Complex / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D018858:Germinal Center / Q000276:immunology*; D007073:Immunoglobulin E / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D007150:Immunohistochemistry; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D010047:Ovalbumin / Q000276:immunology; D017455:Receptors, IgE / Q000276:immunology / Q000378:metabolism; D013154:Spleen / Q000276:immunology*; D014301:Trinitrobenzenes / Q000276:immunology
D000936:Antigen-Antibody Complex; D007074:Immunoglobulin G; D017455:Receptors, IgE; D014301:Trinitrobenzenes; D007073:Immunoglobulin E; D010047:Ovalbumin