Monomeric IgG2a promotes maturation of bone-marrow macrophages and expression of the mannose receptor.
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 Fc gamma-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.
Schreiber
S
S
Division of Gastroenterology, Washington University School of Medicine, St. Louis, MO.
Blum
J S
JS
Stenson
W F
WF
MacDermott
R P
RP
Stahl
P D
PD
Teitelbaum
S L
SL
Perkins
S L
SL
D000818:Animals; D001853:Bone Marrow / Q000276:immunology*; D002453:Cell Cycle; D002478:Cells, Cultured; D007074:Immunoglobulin G / Q000276:immunology*; D007700:Kinetics; D037181:Lectins, C-Type; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D008297:Male; D008358:Mannose / Q000276:immunology; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D051379:Mice; D008805:Mice, Inbred A; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000302:isolation & purification
D007074:Immunoglobulin G; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D008358:Mannose