Themis2 lowers the threshold for B cell activation during positive selection.

Area of Science:

• Immunology
• Molecular Biology
• Cell Signaling

Background:

• Adaptive immunity and self-tolerance rely on lymphocyte selection by antigens.
• The precise mechanisms by which different antigens influence selection are not fully understood.

Purpose of the Study:

• To investigate the role of thymocyte-selection-associated family member 2 (Themis2) in lymphocyte selection and activation.
• To elucidate how Themis2 influences B cell responses to antigens of varying avidity.

Main Methods:

• Investigated the effect of Themis2 on B1 and germinal center B cell selection.
• Assessed B cell activation thresholds in response to low- and high-avidity antigens.
• Examined Themis2 interactions with Grb2, Lyn, and phospholipase γ2 (PLC-γ2).
• Analyzed PLC-γ2 activation and downstream signaling pathways.

Main Results:

• Themis2 was found to increase the positive selection of B1 and germinal center B cells.
• Themis2 lowered the activation threshold for low-avidity antigens but not high-avidity antigens.
• Themis2 constitutively bound Grb2, Lyn, and PLC-γ2.
• Themis2 enhanced PLC-γ2 activation and downstream signaling upon B cell receptor stimulation.

Conclusions:

• Themis2 plays a crucial role in differential B cell signaling, enabling discrimination between antigens.
• Themis2's function provides insight into how B cells differentiate between antigen quantity and quality.
• Themis2 is a key regulator of B cell activation thresholds and selection processes.