title: Human lymphocytes shed a soluble form of CD21 (the C3dg/Epstein-Barr virus receptor, CR2) that binds iC3b and CD23.
abstract: We report on a soluble (s) form of CD21 (the C3dg/Epstein-Barr virus receptor, CR2) that is spontaneously released by B and T lymphocytes. Immunoprecipitation with anti-CD21 mAb of culture supernatants of surface and biosynthetically labeled B and T cell lines revealed a single band with an apparent molecular mass of 135 kDa. The molecule exhibited a molecular mass 10 kDa lower than that of membrane CD21. The release of soluble CD21 (sCD21) was time dependent and correlated with a parallel decrease in the expression of the membrane-associated molecule. The protein was also found in culture supernatants of tonsillar B cells and normal human thymocytes. Epitopic analysis using combinations of anti-CD21 monoclonal antibodies (mAb) indicated that sCD21 and membrane CD21 were similarly recognized by mAb directed against short consensus repeats (SCR) 1-2, SCR 4-5 and SCR 9-11. Affinity-purified sCD21 was capable of binding to purified human iC3b and to human recombinant CD23, as assessed by enzyme-linked immunosorbent assay and by using the BIAcore technology. In addition, normal human serum was found to contain a soluble form of CD21 that exhibited a similar molecular mass to that of the molecule shed by B and T cells in culture. The serum form of CD21 was recognized by all anti-CD21 mAb that we tested and showed a high reactivity with mAb directed against SCR 1-2. Our observations suggest that B and T cells shed the extracellular portion of CD21 and release a soluble molecule that retains the ligand-binding properties of CD21, thus having a potential role in immunoregulation.
authors.affiliation: INSERM U430, Hôpital Broussais, Paris, France.
authors.forename: V
authors.initials: V
authors.lastname: Frémeaux-Bacchi
authors.forename: I
authors.initials: I
authors.lastname: Bernard
authors.forename: F
authors.initials: F
authors.lastname: Maillet
authors.forename: J C
authors.initials: JC
authors.lastname: Mani
authors.forename: M
authors.initials: M
authors.lastname: Fontaine
authors.forename: J Y
authors.initials: JY
authors.lastname: Bonnefoy
authors.forename: M D
authors.initials: MD
authors.lastname: Kazatchkine
authors.forename: E
authors.initials: E
authors.lastname: Fischer
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism*; D003179:Complement C3b / Q000378:metabolism*; D000939:Epitopes / Q000032:analysis; D004854:Herpesvirus 4, Human / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D011485:Protein Binding / Q000276:immunology; D017464:Receptors, Complement 3d / Q000378:metabolism*; D017455:Receptors, IgE / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism*; D012995:Solubility; D013601:T-Lymphocytes / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D000939:Epitopes; D008024:Ligands; D017464:Receptors, Complement 3d; D017455:Receptors, IgE; D011991:Receptors, Virus; D003179:Complement C3b