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 language | English (US) |
|---|---|
| Pages (from-to) | 345-354 |
| Number of pages | 10 |
| Journal | Molecular Immunology |
| Volume | 55 |
| Issue number | 3-4 |
| DOIs | |
| State | Published - Oct 2013 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - A unique form of haptoglobin produced by murine hematopoietic cells supports B-cell survival, differentiation and immune response
AU - Huntoon, Kristin M.
AU - Russell, Lisa
AU - Tracy, Erin
AU - Barbour, Karen W.
AU - Li, Qingsheng
AU - Shrikant, Protul A.
AU - Berger, Franklin G.
AU - Garrett-Sinha, Lee Ann
AU - Baumann, Heinz
PY - 2013/10
Y1 - 2013/10
N2 - 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.
AB - 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.
KW - Acute phase response
KW - Immunoglobin production
KW - Inflammation
UR - http://www.scopus.com/inward/record.url?scp=84877591387&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84877591387&partnerID=8YFLogxK
U2 - 10.1016/j.molimm.2013.03.008
DO - 10.1016/j.molimm.2013.03.008
M3 - Article
C2 - 23548836
AN - SCOPUS:84877591387
VL - 55
SP - 345
EP - 354
JO - Molecular Immunology
JF - Molecular Immunology
SN - 0161-5890
IS - 3-4
ER -