Monomeric IgG2a Promotes Maturation of Bone-Marrow Macrophages and Expression of the Mannose Receptor

• Published in: Proceedings of the National Academy of Sciences - PNAS 1991-03, Vol.88 (5), p.1616-1620
• Main Authors: Schreiber, Stefan, Blum, Janice S., Stenson, William F., MacDermott, Richard P., Stahl, Philip D., Teitelbaum, Steven L., Perkins, Sherrie L.
• Format: Article
• Language: English
• Subjects: 550201 - Biochemistry- Tracer Techniques; ALDEHYDES; ANIMAL CELLS; Animals; Antigens; B lymphocytes; BASIC BIOLOGICAL SCIENCES; BETA DECAY RADIOISOTOPES; Biological and medical sciences; BIOLOGICAL EFFECTS; BIOLOGICAL MATERIALS; BLOOD; BLOOD CELLS; BLOOD COAGULATION FACTORS; BODY FLUIDS; Bone marrow; Bone Marrow - immunology; CARBOHYDRATES; Cell culture techniques; CELL CYCLE; CELL DIFFERENTIATION; Cells, Cultured; COAGULANTS; CONNECTIVE TISSUE CELLS; Cultured cells; DAYS LIVING RADIOISOTOPES; DOSE-RESPONSE RELATIONSHIPS; DRUGS; ELECTRON CAPTURE RADIOISOTOPES; ENZYMES; Fundamental and applied biological sciences. Psychology; Fundamental immunology; GLOBULINS; GLYCOPROTEINS; HEMATOLOGIC AGENTS; HEMOSTATICS; HEXOSES; HYDROLASES; Immunobiology; Immunoglobulin G - immunology; IMMUNOGLOBULINS; IMMUNOLOGY; INTERMEDIATE MASS NUCLEI; INTERNAL CONVERSION RADIOISOTOPES; IODINE 125; IODINE ISOTOPES; ISOTOPE APPLICATIONS; ISOTOPES; Kinetics; Lectins, C-Type; LEUKOCYTES; LYMPHOCYTES; MACROPHAGES; Macrophages - cytology; Macrophages - immunology; Male; MANNOSE; Mannose - immunology; Mannose-Binding Lectins; MATERIALS; Measels mumps rubella vaccine; MEMBRANE PROTEINS; Mice; Mice, Inbred A; Monocytes, macrophages; MONOSACCHARIDES; Myeloid cells: ontogeny, maturation, markers, receptors; NUCLEI; ODD-EVEN NUCLEI; ORGANIC COMPOUNDS; PEPTIDE HYDROLASES; PHAGOCYTES; PROTEINS; RADIOISOTOPES; RADIORECEPTOR ASSAY; RECEPTORS; Receptors, Cell Surface; Receptors, Immunologic - biosynthesis; Receptors, Immunologic - isolation & purification; SACCHARIDES; SERINE PROTEINASES; SOMATIC CELLS; THROMBIN; TRACER TECHNIQUES
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.88.5.1616

The macrophage mannose receptor, a 172-kDa lineage-specific glycoprotein, partakes in nonopsonin-mediated phagocytosis by recognition of terminal mannose residues on targeted particles. Because appearance of the receptor progresses with monocyte/macrophage differentiation, its expression is indicative of the maturational state of the cell. Monomeric IgG2a and IgG2b up-regulate mannose-receptor surface expression and biosynthesis by murine bone-marrow macrophage precursors as much as 7- to 12-fold in a dose-dependent manner. IgG2a accelerates macrophage mannose-receptor expression by several days during in vitro bone-marrow differentiation; however, treated and control cells ultimately express equivalent levels of receptor. Moreover, the effect is independent of cell cycle or ambient levels of colony-stimulating factor 1. The coinduction of another maturation-dependent lineage-specific antigen, F4/80, and the fact that macrophage precursors respond to IgG2a only within the first day of culture, indicate that the targeted cell is an early myelomonocytic precursor, responsive only during a short, early developmental window. The effect is specific for immunoglobulin molecules of the IgG2a and IgG2b subclasses and probably involves an Fcγ-receptor signal-transduction pathway but not macrophage priming or activation. Most importantly, a paracrine mechanism of immunoglobulin-mediated bone-marrow macrophage differentiation is suggested by experiments in which basal levels of mannose-receptor expression are reduced by continual removal of B-cell-generated IgG from marrow cultures. Thus, IgG2a and IgG2b prompt mannose-receptor synthesis and bone-marrow macrophage differentiation and may, therefore, play a role in the regulation of macrophage differentiation in host defense.