title: Reconstitution of the complement function in C1q-deficient (C1qa-/-) mice with wild-type bone marrow cells.
abstract: Besides Ab-independent and Ab-dependent activation of the complement classical pathway in host defense, C1q plays a key role in the processing of immune complexes and in the clearance of apoptotic cells. In humans, C1q deficiency leads to systemic lupus erythematosus-like symptoms in over 90% of the cases, thus making this defect a strong disease susceptibility factor. Similarly, C1q-deficient mice (C1qa-/-) develop systemic lupus erythematosus-like symptoms, such as autoantibodies and glomerulonephritis. We have previously provided evidence that C1q is produced by cells of the monocyte-macrophage lineage. In this study, we have tested whether transplantation of bone marrow cells would be sufficient to reconstitute C1q levels in C1qa-/- mice. C1qa-/- mice received a single graft of 10(7) bone marrow cells from wild-type (wt) donors after irradiation doses of 6, 7, 8, or 9 Gy. Engraftment was monitored by a Y chromosome-specific PCR and a PCR that differentiated wt from C1qa-/- genotype. Serum levels of C1q Ag and C1 function increased rapidly in the recipient mice, and titers reached normal levels within 6 wk after bone marrow transplantation. In wt mice that received C1qa-/- bone marrow, serum levels of C1q decreased constantly over time and became C1q deficient within 55 wk. These data clearly demonstrate that bone marrow-derived cells are the source of serum C1q and are competent to reconstitute normal C1q serum levels in C1q-deficient mice. Therefore, stem cell transplantation could be a therapy for patients with hereditary C1q deficiency.
authors.affiliation: Institute of Medical Microbiology and Hygiene and Institute of Virology, Johannes Gutenberg-University, Augustusplatz/Hochhaus, D-55101 Mainz, Germany. fpetry@mail.uni-mainz.de
authors.forename: F
authors.initials: F
authors.lastname: Petry
authors.forename: M
authors.initials: M
authors.lastname: Botto
authors.forename: R
authors.initials: R
authors.lastname: Holtappels
authors.forename: M J
authors.initials: MJ
authors.lastname: Walport
authors.forename: M
authors.initials: M
authors.lastname: Loos
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D015922:Complement C1q / Q000172:deficiency / Q000235:genetics* / Q000502:physiology*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D007700:Kinetics; D008180:Lupus Erythematosus, Systemic / Q000628:therapy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000096:biosynthesis; D014018:Tissue Distribution; D014998:Y Chromosome
chemical_list: D012333:RNA, Messenger; D015922:Complement C1q