Enhanced adaptive immunity in mice lacking the immunoinhibitory adaptor Hacs1

Dingyan Wang, A. Keith Stewart, Lihua Zhuang, Yuanxiao Zhu, Youdong Wang, Changxin Shi, Armand Keating, Arthur Slutsky, Haibo Zhang, Xiao Yan Wen

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)947-956
Number of pages10
JournalFASEB Journal
Volume24
Issue number3
DOIs
StatePublished - Mar 1 2010

Keywords

  • Adaptor protein
  • B cells
  • Dendritic cells
  • Gene targeting
  • Immune regulation
  • SAM domain

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Fingerprint Dive into the research topics of 'Enhanced adaptive immunity in mice lacking the immunoinhibitory adaptor Hacs1'. Together they form a unique fingerprint.

Cite this