T_FH-derived dopamine accelerates productive synapses in germinal centres

Area of Science:

• Immunology
• Neuroscience
• Cell Biology

Background:

• Protective antibody responses rely on B cell selection by follicular helper T (T_FH) cells in germinal centers.
• T_FH cell interactions with B cells resemble neural synaptic transmission.

Purpose of the Study:

• To investigate the presence of neuronal markers in human T_FH cells.
• To explore the role of dopamine in T_FH-B cell interactions and germinal center responses.

Main Methods:

• Immunohistochemistry to detect chromogranin B in T_FH cells.
• Measurement of dopamine production and release by T_FH cells.
• Analysis of ICOSL and CD40L translocation on B cells.
• Mathematical modeling of T-B cell interaction dynamics.

Main Results:

• Human T_FH cells contain dense-core granules with chromogranin B, a neuronal marker.
• T_FH cells produce and release dopamine upon interaction with B cells.
• Dopamine signaling rapidly enhances T_FH-B cell synapse formation and function.
• Mathematical modeling indicates accelerated germinal center reactions due to dopamine.

Conclusions:

• Follicular helper T cells utilize dopamine, a neurotransmitter, to modulate B cell selection and antibody production.
• Neurotransmitter delivery across the T-B cell synapse represents a novel mechanism for enhancing immune responses.
• This pathway may accelerate adaptive immunity, offering advantages during infections.