期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 44, 期 11, 页码 3206-3219出版社
WILEY
DOI: 10.1002/eji.201444479
关键词
Germinal center; IgE; Nippostrongylus brasiliensis; Plasma cell; Swiprosin-1; EFhd2
类别
资金
- German Science Foundation (Deutsche Forschungsgemeinschaft, DFG) [FOR832, GK1660]
- Interdisciplinary Clinical Research Center Erlangen (IZKF) [E8]
- ERC starting grant from the European Union [PAS 241506]
- NIH [U01HG004085]
- CSD Consortium [U01HG004080]
- Austrian Science Fund (FWF) [E8] Funding Source: Austrian Science Fund (FWF)
Activated Bcells are selected for in germinal centers by regulation of their apoptosis. The Ca2+-binding cytoskeletal adaptor protein Swiprosin-1/EFhd2 (EFhd2) can promote apoptosis in activated Bcells. We therefore hypothesized that EFhd2 might limit humoral immunity by repressing both the germinal center reaction and the expected enhancement of immune responses in the absence of EFhd2. Here, we established EFhd2(-/-) mice on a C57BL/6 background, which revealed normal B- and T-cell development, basal Ab levels, and T-cell independent type 1, and T-cell independent type 2 responses. However, Tcell-dependent immunization with sheep red blood cells and infection with the helminth Nippostrongylus brasiliensis (N.b) increased production of antibodies of multiple isotypes, as well as germinal center formation in EFhd2(-/-) mice. In addition, serum IgE levels and numbers of IgE(+) plasma cells were strongly increased in EFhd2(-/-) mice, both after primary as well as after secondary N.b infection. Finally, mixed bone marrow chimeras unraveled an EFhd2-dependent Bcell-intrinsic contribution to increased IgE plasma cell numbers in N.b-infected mice. Hence, we established a role for EFhd2 as a negative regulator of germinal center-dependent humoral type 2 immunity, with implications for the generation of IgE.
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