Unique Maturation Program of the IgE Response In Vivo

Immunity 26: 191-203(2007)

Speaker: 蔡明勳                                            Time: 14:00-15:00, 05/30, 2007

Commentator: 王志堯 老師                         Place: Room 601

Abstract

The IgE antibodies production plays a major role in some allergies. Although the IgE response is important, it is not clear about the mechanism of IgE class-switching, the biology of IgE+ cells, and even whether memory IgE+ cells exist. The major reason is the low frequency of IgE+ cells in vivo. In previous studies, the authors produced a high-IgE production T/B monoclonal mouse model by nuclear-transplantation cloning technology. Therefore, they used this model and helminth infected BALB/c mice to study IgE response. At first, the authors investigated the localization of IgE+ cells after immunization with Ag (OVA-HA). Unexpectedly, the majority of IgE+ cells were found outside germinal center (GC) in which conventionally class-switching take place. However, by analyzingεtranscripts amounts and immunohistology, the authors speculated that class switching to IgE initiates in GC stage. To circumvent the problem why the switched IgE+ cells run out of GC, they isolated IgE+ cells and typed cells. The result showed that IgE+ cells display a plasma cell phenotype. Moreover, by immunization of a low affinity variant Ag(OVA-PEP), the authors demonstrated that IgE antibodies undergo somatic hypermutation and affinity maturation even though the lack of GC localization. Therefore, they hypothesized that IgE⁺ cells may not undergo somatic hypermutation and affinity maturation, but rather they could inherit mutated and selected VDJ genes from precursor IgG1⁺ cells. By adoptive transfer of IgG1+ cells, they demonstrated that memory IgG1+ B cells are able to generate a high-affinity IgE response by sequential switching. In addition, de novo production of IgE in the in vitro culture showed further that production of IgE in cultures of IgG1⁺ cells was dependent upon stimulation with CD40 antibodies and IL-4, but profoundly suppressed by IL-21.

Reference

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