Two 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 protein (p70) were isolated from Staphylococcus aureus by ion exchange chromatography. We compared their properties to those of the well established B cell mitogen of whole, fixed Staph. aureus strain Cowan I cells (SAC). Both purified proteins were able to induce immunoglobulin synthesis in PBMC cultures of healthy donors. NP-tase and p70 also induced immunoglobulin synthesis of PBMC from those patients with CVID who were also responsive to SAC plus IL-2 stimulation. Immunoglobulin synthesis in response to NP-tase and to p70 was time- and dose-dependent and could be inhibited by addition of specific antibodies against the proteins. In contrast to SAC, no addition of exogenous IL-2 was necessary 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 supernatants of PBMC from healthy donors following stimulation with low concentrations of NP-tase or p70, and this was associated with vigorous lymphocyte proliferation. Both proteins behave like typical antigens, and not like lectins or superantigens, since an NP-tase-stimulated T cell line showed an antigen-specific, MHC-restricted secondary response. In addition, no preferential T cell receptor V beta chain usage was found with eight V beta-specific MoAb. It is likely that the two proteins induce antigen-specific T cell activation, which is then followed by polyclonal activation of B cells via CD40 receptors and cytokine release.
Jahreis
A
A
Department of Internal Medicine, University Hospital Freiburg, Germany.
Yousif
Y
Y
Rump
J A
JA
Dräger
R
R
Vogt
A
A
Peter
H H
HH
Schlesier
M
M
D000328:Adult; D000917:Antibody Formation; D000942:Antigens, Bacterial / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D001426:Bacterial Proteins / Q000737:chemistry / Q000276:immunology; D002412:Cations; D002478:Cells, Cultured; D017074:Common Variable Immunodeficiency / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007156:Immunologic Memory; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008213:Lymphocyte Activation; D010744:Phosphoric Monoester Hydrolases / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D002412:Cations; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007376:Interleukin-2; C092526:Staphylococcal neutral phosphatase; D010744:Phosphoric Monoester Hydrolases