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

作者：Huntoon Kristin M; Russell Lisa; Tracy Erin; Barbour Karen W; Li Qingsheng; Shrikant Protul A; Berger Franklin G; Garrett Sinha Lee Ann; Baumann Heinz^*

来源：Molecular Immunology, 2013, 55(3-4): 345-354.

DOI：10.1016/j.molimm.2013.03.008

• Acute phase response
• Inflammation
• Immunoglobin production

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.

• 出版日期2013-10