Macrophage-derived complement component C4 can restore humoral immunity in C4-deficient mice

Mihaela Gadjeva, Admar Verschoor, Mark A. Brockman, Heather Jezak, Li Ming Shen, David M. Knipe, Michael C. Carroll*

*Corresponding author for this work
33 Citations (Scopus)


Mice with a disrupted C4 locus (C4-/-) have an impaired immune response to thymus-dependent Ags. To test the role of bone marrow-derived C4 in humoral immunity, we reconstituted deficient animals with wild-type bone marrow or an enriched fraction of bone marrow-derived macrophages. C4 chimeras were immunized with 4-hydroxy-3-nitrophenyl5 conjugated to keyhole limpet hemocyanin (NP5-KLH) or infected with HSV-1, and the Ab response was evaluated. Wild-type bone marrow rescued the humoral immune response to both Ags, i.e., the soluble Ag and HSV-1, demonstrating that local C4 production is sufficient for humoral responses. Although the C4 chimeric animals lacked detectable C4 in their sera, C4 mRNA was identified in splenic sections by in situ hybridization, and C4 protein deposits were identified in the germinal center areas of splenic follicles by immunofluorescence staining. Macrophages derived from bone marrow produced sufficient C4 protein to restore the humoral response to NP5-KLH in C4-deficient animals when administered along with Ag. Cell-sorting experiments, followed by C4-specific RT-PCR, identified splenic macrophages (CD11b+, CD11c-) as a cellular source for C4 synthesis within the spleen.

Original languageEnglish
JournalJournal of Immunology
Issue number10
Pages (from-to)5489-5495
Number of pages7
Publication statusPublished - 15.11.2002

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)


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