A unique form of haptoglobin produced by murine hematopoietic cells supports B-cell survival, differentiation and immune response

Kristin M. Huntoon, Lisa Russell, Erin Tracy, Karen W. Barbour, Qingsheng Li, Protul A. Shrikant, Franklin G. Berger, Lee Ann Garrett-Sinha, Heinz Baumann

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Haptoglobin (Hp), an acute phase reactant and major hemoglobin-binding protein, has a unique role in host immunity. Previously, we demonstrated that Hp-deficient C57BL/6J mice exhibit stunted development of mature T- and B-cells resulting in markedly lower levels of antigen-specific IgG. The current study identified leukocyte-derived pro-Hp as a relevant mediator of an optimal immune response. Reconstitution of Hp-/- mice with Hp+/+ bone marrow restored normal immune response to ovalbumin. Furthermore, transplanting a mixture of bone marrow-derived from B-cell-deficient and Hp-deficient mice into Rag1-/-/Hp+/+ recipients resulted in mice with a defective immune response similar to Hp-/- mice. This suggests that Hp generated by the B-cell compartment, rather than by the liver, is functionally contributing to a normal immune response. Leukocytes isolated from the spleen express Hp and release a non-proteolytically processed pro-Hp that uniquely differed from liver-derived Hp by not binding to hemoglobin. While addition of purified plasma Hp to cultured B-cells did not alter responses, pro-Hp isolated from splenocytes enhanced cellular proliferation and production of IgG. Collectively, the comparison of wild-type and Hp-deficient mice suggests a novel regulatory activity for lymphocyte-derived Hp, including Hp produced by B-cells themselves, that supports in vivo survival and functional differentiation of the B-cells to ensure an optimal immune response.

Original languageEnglish (US)
Pages (from-to)345-354
Number of pages10
JournalMolecular Immunology
Volume55
Issue number3-4
DOIs
StatePublished - Oct 2013

Keywords

  • Acute phase response
  • Immunoglobin production
  • Inflammation

ASJC Scopus subject areas

  • Immunology
  • Molecular Biology

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    Huntoon, K. M., Russell, L., Tracy, E., Barbour, K. W., Li, Q., Shrikant, P. A., Berger, F. G., Garrett-Sinha, L. A., & Baumann, H. (2013). A unique form of haptoglobin produced by murine hematopoietic cells supports B-cell survival, differentiation and immune response. Molecular Immunology, 55(3-4), 345-354. https://doi.org/10.1016/j.molimm.2013.03.008