2 NOVEL CATIONIC STAPHYLOCOCCAL PROTEINS INDUCE IL-2 SECRETION, PROLIFERATION AND IMMUNOGLOBULIN-SYNTHESIS IN PERIPHERAL-BLOOD MONONUCLEAR-CELLS (PBMC) OF BOTH HEALTHY CONTROLS AND PATIENTS WITH COMMON VARIABLE IMMUNODEFICIENCY (CVID)

Two cationic proteins, a neutral phosphatase (NP-tase) and a 70-kD pro tein (p70) were isolated from Staphylococcus aureus by ion exchange ch romatography. We compared their properties to those of the well establ ished B cell mitogen of whole, fixed Staph. aureus strain Cowan I cell s (SAG). Both purified proteins were able to induce immunoglobulin syn thesis in PBMC cultures of healthy donors. NP-tase and p70 also induce d immunoglobulin synthesis of PBMC from those patients with CVID who w ere also responsive to SAC plus IL-2 stimulation. Immunoglobulin synth esis in response to NP-tase and to p70 was time- and dose-dependent an d could be inhibited by addition of specific antibodies against the pr oteins. In contrast to SAG, no addition of exogenous IL-2 was necessar y to obtain maximal immunoglobulin synthesis induced by NP-tase or p70 . However, neither protein was able to induce immunoglobulin synthesis in B cell-enriched cultures. High amounts of IL-2 were found in super natants of PBMC from healthy donors following stimulation with low con centrations of NP-tase or p70, and this was associated with vigorous l ymphocyte proliferation. Both proteins behave like typical antigens, a nd not like lectins or superantigens, since an NP-tase-stimulated T ce ll line showed an antigen-specific, MHC-restricted secondary response. In addition, no preferential T cell receptor V beta chain usage was f ound with eight V beta-specific MoAb. It is likely that the two protei ns induce antigen-specific T cell activation, which is then followed b y polyclonal activation of B cells via CD40 receptors and cytokine rel ease.