| Autor: |
Asrat, Seblewongel, Kaur, Navneet, Liu, Xia, Ben, Li-Hong, Kajimura, Daisuke, Murphy, Andrew J., Sleeman, Matthew A., Limnander, Andre, Orengo, Jamie M. |
| Zdroj: |
Science Immunology; 2020, Vol. 5 Issue 43, p1-16, 16p |
| Abstrakt: |
Locating the reservoir for IgE memory: Allergic diseases persist when the immune system chronically churns out allergen-specific IgE antibodies. Identifying the tissue location of IgE+ memory plasma cells is complicated by their very low frequency. Asrat et al. tracked IgE+ memory plasma cell development after intranasal exposure of mice to house dust mite allergen using fluorescent reporter transgenes to mark IgE+ plasma cells. In mice repeatedly exposed to allergen for 15 weeks, long-lived IgE+ memory plasma cells emerged in the bone marrow. IgE+ memory plasma cells in the bone marrow of both mice and allergic human patients yielded pathogenic IgE antibodies capable of eliciting anaphylaxis after transfer. Identification of long-lived plasma cells as the chief source of IgE memory may assist in developing new therapeutic approaches for chronic allergic diseases. Immunoglobulin E (IgE) plays an important role in allergic diseases. Nevertheless, the source of IgE serological memory remains controversial. We reexamined the mechanism of serological memory in allergy using a dual reporter system to track IgE+ plasma cells in mice. Short-term allergen exposure resulted in the generation of IgE+ plasma cells that resided mainly in secondary lymphoid organs and produced IgE that was unable to degranulate mast cells. In contrast, chronic allergen exposure led to the generation of long-lived IgE+ plasma cells that were primarily derived from sequential class switching of IgG1, accumulated in the bone marrow, and produced IgE capable of inducing anaphylaxis. IgE+ plasma cells were found in the bone marrow of human allergic, but not nonallergic donors, and allergen-specific IgE produced by these cells was able to induce mast cell degranulation when transferred to mice. These data demonstrate that long-lived IgE+ bone marrow plasma cells arise during chronic allergen exposure and establish serological memory in both mice and humans. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
