mTECs and B cells form a thymic microniche associated with B-cell licensing

Area of Science:

• Immunology
• Cell Biology
• Thymic Development

Background:

• Thymic B cells require T cells and type-III interferon (IFN-λ) for licensing as antigen-presenting cells (APCs), crucial for central T-cell tolerance.
• IFN-λ is produced by medullary thymic epithelial cells (mTECs), but the spatial relationship between B cells and IFN-λ-producing mTECs is not fully understood.

Purpose of the Study:

• To investigate the spatial distribution of thymic B cells and IFN-λ-producing mTECs.
• To elucidate the niche requirements for thymic B-cell licensing and the role of specific mTEC subsets.

Main Methods:

• Multiplex immunofluorescence imaging (26 targets) to identify and map thymic cell populations.
• Spatial analysis to determine proximity between B cells and mTECs.
• Analysis of CCR6-deficient mice and NOD/ShiLtJ mice with reduced microfold mTECs.

Main Results:

• Licensed B cells were found in close proximity to IFN-λ+ mTECs and GP2+ microfold mTECs.
• Transcriptional analysis suggested CCL20-CCR6 interactions, but CCR6 deficiency did not impair B-cell licensing.
• NOD mice with fewer microfold mTECs showed reduced B-cell licensing, linked to decreased IFN-λ receptor expression on B cells.

Conclusions:

• Microfold mTECs modulate thymic B-cell licensing capacity.
• This modulation occurs through influencing IFN-λ receptor expression on B cells, impacting their ability to respond to IFN-λ signaling.
• Understanding these interactions is key to comprehending central T-cell tolerance mechanisms.