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Enhanced adaptive immunity in mice lacking the immunoinhibitory adaptor Hacs1.
- Source :
-
FASEB Journal . Mar2010, Vol. 24 Issue 3, p947-956. 10p. 3 Diagrams, 3 Graphs. - Publication Year :
- 2010
-
Abstract
- Hacs1, a SH3 and SAM domain-containing adaptor protein, is up-regulated by IL-4 in activated B cells and strongly expressed in dendritic cells. To elucidate the function of Hacs1 in immune regulation, we generated Hacs1-/- mice by deletion of the SH3 and SAM domains. Hacs1-/- mice were viable and fertile and had normal bone marrow B-cell development and normal splenic T- and B-cell populations. However, adult Hacs1-/- mice had increased peritoneal B1a cells (IgM+CD5+). On immunization with T-cell-independent antigen TNP-Ficoll, Hacs1-/- mice had increased production of anti-TNP IgM and IgG3. Purified splenic B cells from Hacs1-/- mice showed increased cell proliferation on BCR (B-cell receptor) stimulation. We further demonstrate that the Hacs1-/- B cells had increased global tyrosine phosphorylation, including tyrosine kinases Lyn and Akt. Both T-helper type 1 (Th1) and T-helper type 2 (Th2) humoral responses were enhanced in Hacs1-/- mice. In vitro bone marrow-derived Hacs1-/- dendritic cells showed increased IL-12 production on stimulation with ovalbumin (OVA). This study suggests that Hacs1 is an immunoinhibitory adaptor that might be a useful target for immune suppression therapy. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 08926638
- Volume :
- 24
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- FASEB Journal
- Publication Type :
- Academic Journal
- Accession number :
- 48549309
- Full Text :
- https://doi.org/10.1096/fj.09-140806