Binding site for IgE of the human lymphocyte low-affinity Fc epsilon receptor (Fc epsilon RII/CD23) is confined to the domain homologous with animal lectins.
The lymphocyte low-affinity receptor for IgE (Fc epsilon RII) is involved in two seemingly unrelated processes: (i) promotion of general B-cell growth and (ii) isotype-specific IgE synthesis. To characterize domains of Fc epsilon RII important for effector function, we have expressed Fc epsilon RII mutants in mammalian cells. The results show that the IgE-binding region of Fc epsilon RII corresponds almost exactly to a domain of 123 amino acid residues homologous with the carbohydrate-binding domain of C-type animal lectins. With the recent demonstration that Fc epsilon RII binds to IgE independently of any lectin-like activity [Vercelli, D., Helm, B., Marsh, P., Padlan, E., Geha, R.S. & Gould, H. (1989) Nature (London) 338, 649-651], it is now clear that, in this case, the lectin module has evolved to interact with a protein rather than a carbohydrate moiety. The epitopes of several independent monoclonal antibodies that inhibit the binding of IgE to Fc epsilon RII are clustered within the lectin-like domain. Some of these antibodies are also known to suppress, isotype-specifically, the interleukin 4-promoted IgE synthesis from peripheral blood mononuclear cells or the spontaneous synthesis of IgE by B cells isolated from atopic donors. The epitope of MHM6, an anti-F epsilon RII monoclonal antibody delivering an epitope-restricted growth-promoting effect on B cells, is also located within the lectin-like domain. Thus, the lectin module of Fc epsilon RII not only acts as a carbohydrate-independent, isotype-specific Fc receptor but may also participate in the general regulation of B-cell growth.
Bettler
B
B
Department of Biotechnology, Ciba-Geigy Ltd., Basel, Switzerland.
Maier
R
R
Rüegg
D
D
Hofstetter
H
H
D000818:Animals; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D002872:Chromosome Deletion; D000939:Epitopes / Q000032:analysis; D005796:Genes; D005822:Genetic Vectors; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism*; D037102:Lectins / Q000235:genetics*; D008214:Lymphocytes / Q000276:immunology*; D009154:Mutation; D011961:Receptors, Fc / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D017455:Receptors, IgE; D012689:Sequence Homology, Nucleic Acid; D014162:Transfection
D000911:Antibodies, Monoclonal; D000944:Antigens, Differentiation, B-Lymphocyte; D000939:Epitopes; D037102:Lectins; D011961:Receptors, Fc; D017455:Receptors, IgE; D007073:Immunoglobulin E