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

4 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Haptoglobins
Cell Differentiation
Cell Survival
B-Lymphocytes
Hemoglobins
Leukocytes
Immunoglobulin G
Bone Marrow
Acute-Phase Proteins
Liver
Ovalbumin

Keywords

  • Acute phase response
  • Immunoglobin production
  • Inflammation

ASJC Scopus subject areas

  • Molecular Biology
  • Immunology

Cite this

A unique form of haptoglobin produced by murine hematopoietic cells supports B-cell survival, differentiation and immune response. / Huntoon, Kristin M.; Russell, Lisa; Tracy, Erin; Barbour, Karen W.; Li, Qingsheng; Shrikant, Protul A.; Berger, Franklin G.; Garrett-Sinha, Lee Ann; Baumann, Heinz.

In: Molecular Immunology, Vol. 55, No. 3-4, 10.2013, p. 345-354.

Research output: Contribution to journalArticle

Huntoon, KM, Russell, L, Tracy, E, Barbour, KW, Li, Q, Shrikant, PA, Berger, FG, Garrett-Sinha, LA & Baumann, H 2013, 'A unique form of haptoglobin produced by murine hematopoietic cells supports B-cell survival, differentiation and immune response', Molecular Immunology, vol. 55, no. 3-4, pp. 345-354. https://doi.org/10.1016/j.molimm.2013.03.008
Huntoon, Kristin M. ; Russell, Lisa ; Tracy, Erin ; Barbour, Karen W. ; Li, Qingsheng ; Shrikant, Protul A. ; Berger, Franklin G. ; Garrett-Sinha, Lee Ann ; Baumann, Heinz. / A unique form of haptoglobin produced by murine hematopoietic cells supports B-cell survival, differentiation and immune response. In: Molecular Immunology. 2013 ; Vol. 55, No. 3-4. pp. 345-354.
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