Soluble CD16 binds peripheral blood mononuclear cells and inhibits pokeweed-mitogen-induced responses.
Human neutrophils express two types of low affinity receptors for IgG, Fc gamma RII or CD32 and Fc gamma RIIIB or CD16. Human serum contains soluble CD16 (sCD16), which is produced by proteolysis of neutrophil Fc gamma RIIIB, the cleavage site being located close to the cell surface. In order to assess the functional roles of sCD16, we have produced, in eukaryotic cells, a recombinant sCD16 containing the extracellular region of Fc gamma RIIIB. Purified sCD16, of molecular mass of 48 kD, bound human IgG1 and IgG3 but not IgG2, IgG4, or F(ab')2. It inhibited, in a time and dose-dependent fashion, proliferation and IgM and IgG production of human peripheral blood mononuclear cells (PBMC) stimulated by pokeweed mitogen (PWM) in vitro. FACS analysis showed that biotinylated sCD16 bound specifically to a fraction (35%) of PBMC, which corresponds to monocytes and to subsets of B and T lymphocytes. Moreover, sCD16 did not modify the staining of PBMC by FITC-coupled PWM. Thus, the biologic function(s) of sCD16 on PWM-induced responses are exerted through direct and specific interaction(s) with mononuclear blood cells and not with PWM. In conclusion, neutrophils may play a regulatory role on immune responses via the production of soluble forms of CD16 with cell-binding and antiproliferative capacities.
Teillaud
C
C
Laboratoire d'Immunologie Cellulaire et Clinique, Unité INSERM 255, Institut Curie, Paris, France.
Galon
J
J
Zilber
M T
MT
Mazières
N
N
Spagnoli
R
R
Kurrle
R
R
Fridman
W H
WH
Sautès
C
C
D001483:Base Sequence; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000032:analysis; D007136:Immunoglobulins / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D011043:Pokeweed Mitogens / Q000494:pharmacology; D017452:Receptors, IgG / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology
D007132:Immunoglobulin Isotypes; D007136:Immunoglobulins; D011043:Pokeweed Mitogens; D017452:Receptors, IgG; D011994:Recombinant Proteins