Universität zu Köln

Brachs, Sebastian ORCID: 0000-0002-6336-3939, Turqueti-Neves, Adriana, Stein, Merle ORCID: 0000-0003-2926-6219, Reimer, Dorothea, Brachvogel, Bent, Boesl, Michael, Winkler, Thomas, Voehringer, David, Jaeck, Hans-Martin and Mielenz, Dirk (2014). Swiprosin-1/EFhd2 limits germinal center responses and humoral type 2 immunity. Eur. J. Immunol., 44 (11). S. 3206 - 3220. HOBOKEN: WILEY. ISSN 1521-4141

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Brachs, Sebastian UNSPECIFIED orcid.org/0000-0002-6336-3939 UNSPECIFIED Turqueti-Neves, Adriana UNSPECIFIED UNSPECIFIED UNSPECIFIED Stein, Merle UNSPECIFIED orcid.org/0000-0003-2926-6219 UNSPECIFIED Reimer, Dorothea UNSPECIFIED UNSPECIFIED UNSPECIFIED Brachvogel, Bent UNSPECIFIED UNSPECIFIED UNSPECIFIED Boesl, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Winkler, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Voehringer, David UNSPECIFIED UNSPECIFIED UNSPECIFIED Jaeck, Hans-Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Mielenz, Dirk UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-424199
DOI:	10.1002/eji.201444479
Journal or Publication Title:	Eur. J. Immunol.
Volume:	44
Number:	11
Page Range:	S. 3206 - 3220
Date:	2014
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1521-4141
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language B-CELLS; MICROCLUSTER FORMATION; ANTIGEN RECEPTORS; IGE RESPONSE; IN-VIVO; LYMPHOCYTES; MICE; SELECTION; DYNAMICS; BCR Multiple languages Immunology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/42419