title: A unique form of haptoglobin produced by murine hematopoietic cells supports B-cell survival, differentiation and immune response.
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.
authors.affiliation: Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.
authors.forename: Kristin M
authors.initials: KM
authors.lastname: Huntoon
authors.forename: Lisa
authors.initials: L
authors.lastname: Russell
authors.forename: Erin
authors.initials: E
authors.lastname: Tracy
authors.forename: Karen W
authors.initials: KW
authors.lastname: Barbour
authors.forename: Qingsheng
authors.initials: Q
authors.lastname: Li
authors.forename: Protul A
authors.initials: PA
authors.lastname: Shrikant
authors.forename: Franklin G
authors.initials: FG
authors.lastname: Berger
authors.forename: Lee Ann
authors.initials: LA
authors.lastname: Garrett-Sinha
authors.forename: Heinz
authors.initials: H
authors.lastname: Baumann
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000276:immunology* / Q000378:metabolism; D016026:Bone Marrow Transplantation / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D006242:Haptoglobins / Q000096:biosynthesis / Q000172:deficiency / Q000502:physiology*; D008099:Liver / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018183:Transplantation Chimera / Q000276:immunology
chemical_list: D006242:Haptoglobins
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