Recombinant soluble receptors for the Fc gamma portion inhibit antibody production in vitro.
The problem of the structural relationship between suppressive IgG-binding factor and low-affinity receptors for the Fc portion of IgG (Fc gamma RII) has not yet been solved. In the present work we have isolated a recombinant soluble Fc gamma RII containing only the two external domains of Fc gamma RII, and analyzed its biochemical characteristics and biological activity. A cDNA encoding Fc gamma RII was mutated by the creation of a stop codon at the Lys175 codon. L cells have been transfected with this cDNA inserted into an expression vector. A cell line was obtained that secretes recombinant soluble Fc gamma RII which reacts with a monoclonal anti-Fc gamma RII antibody and binds to IgG1, IgG2a and IgG2b murine isotypes but not to IgG3 or F(ab')2 fragments of IgG2a. The secreted molecule contains two molecular species of relative molecular mass (Mr) 44,000 and 34,000-38,000 and of pI 4.5 and 6.3. They correspond to different glycosylations of a single polypeptide of Mr 19,000. After purification to homogeneity, soluble Fc gamma RII has found to suppress secondary and primary in vitro antibody responses in a dose-dependent way. The present work shows that recombinant soluble Fc gamma RII has biochemical characteristics, immunoreactivity and biological activity similar to those of suppressive IgG-binding factor.
Varin
N
N
Institut Curie, Paris, France.
Sautès
C
C
Galinha
A
A
Even
J
J
Hogarth
P M
PM
Fridman
W H
WH
D000917:Antibody Formation; D000943:Antigens, Differentiation / Q000502:physiology*; D004252:DNA Mutational Analysis; D004306:Dose-Response Relationship, Immunologic; D007074:Immunoglobulin G / Q000502:physiology*; D007156:Immunologic Memory; D066298:In Vitro Techniques; D007739:L Cells; D008222:Lymphokines / Q000502:physiology; D029584:Prostatic Secretory Proteins; D011961:Receptors, Fc / Q000502:physiology*; D017452:Receptors, IgG; D011994:Recombinant Proteins; D012995:Solubility; D013329:Structure-Activity Relationship; D013491:Suppressor Factors, Immunologic
D000943:Antigens, Differentiation; D007074:Immunoglobulin G; D008222:Lymphokines; D029584:Prostatic Secretory Proteins; D011961:Receptors, Fc; D017452:Receptors, IgG; D011994:Recombinant Proteins; D013491:Suppressor Factors, Immunologic; C043076:beta-microseminoprotein; C013059:immunoglobulin-binding factors