Human T cell-dependent B cell differentiation induced by staphylococcal superantigens

Area of Science:

• Immunology
• Microbiology

Background:

• Microbial superantigens (SAgs) activate T cells by binding TCR V beta and MHC class II molecules.
• Inducing Ig production in SAg-stimulated cultures typically requires T cell manipulation, unlike anti-CD3 mAb stimulation.

Purpose of the Study:

• To investigate if SAgs can induce T cell-dependent B cell differentiation in unmanipulated peripheral blood and tonsil T cells.
• To elucidate the cellular requirements and molecular mechanisms involved in SAg-induced B cell differentiation.

Main Methods:

• Utilized eight different staphylococcal SAgs to stimulate unmanipulated peripheral blood and tonsil T cells.
• Assessed T cell-dependent B cell differentiation and Ig-secreting cell (IgSC) generation.
• Investigated the role of accessory cells (AC) and CTLA4Ig inhibition.

Main Results:

• SAgs, at lower concentrations than required for proliferation, triggered polyclonal B cell differentiation in unmanipulated T cells.
• SAg-induced IgSC generation required only T cells and B cells, functioning without monocytes if B cells acted as accessory cells.
• Physical contact between T cells, B cells, and AC was necessary.
• CTLA4Ig dose-dependently inhibited SAg-induced IgSC generation, with minimal effect on T cell proliferation, indicating CD28/B7 pathway importance.

Conclusions:

• SAg-induced T cell-dependent B cell differentiation is a robust model for studying T cell/B cell interactions, requiring only T cells and B cells.
• CD28 (CTLA4)/B7 (B7-like) dependent mechanisms are crucial for SAg-induced IgSC generation.