HUMAN LYMPHOCYTE SHED A SOLUBLE FORM OF CD21 (THE C3DG EPSTEIN-BARR VIRUS RECEPTOR, CR-2) THAT BINDS IC3B AND CD23/

We report on a soluble (s) form of CD21 (the C3dg/Epstein-Barr virus r eceptor, CR2) that is spontaneously released by B and T lymphocytes. I mmunoprecipitation with anti-CD21 mAb of culture supernatants of surfa ce and biosynthetically labeled B and T cell lines revealed a single b and 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 para llel decrease in the expression of the membrane-associated molecule. T he 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 membran e CD21 were similarly recognized by mAb directed against short concens us repeats (SCR) 1-2, SCR 4-5 and SCR 9-11. Affinity-purified sCD21 wa s capable of binding to purified human iC3b and to human recombinant C D23, as assessed by enzyme-linked immunosorbent assay and by using the BIACore(TM) 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 f orm of CD21 was recognized by all anti-CD21 mAb that we tested and sho wed a high reactivity with mAb directed against SCR 1-2. Our observati ons suggest that B and T cells shed the extracellular portion of CD21 and release a soluble molecule that retains the ligand-binding propert ies of CD21, thus having a potential role in immunoregulation.