Thymic mimetic cells are chimeras between medullary-thymic-epithelial cells (mTECs) and peripheral cell types. Huisman, Michelson, et al. perform high-resolution profiling of human mimetics, revealing a diversification of nerve and ionocyte mTECs and a massive expansion of muscle mTECs vis-à-vis mice. Comparison of human, mouse, and zebrafish mimetics reveals species-specific and species-conserved subtypes.

Aberrant immune signal strength in B cells is associated with autoimmune diseases and lymphoma. Diehl et al. show that hyperreactive B cells trigger cytotoxic T cell-mediated elimination. Less reactive B cells escape this tolerance mechanism, revealing a narrow reactivity window for the emergence of autoimmunity.

The balance of T cells in a progenitor-exhausted state and those in a terminally exhausted state is a critical determinant of anti-tumor responses. Waibl Polania, Hoyt-Miggelbrink, et al. identify antigen presentation and tumor-associated macrophages (TAMs) as key drivers of counterproductive skews toward terminal exhaustion in solid tumors. TAM depletion restores this balance and enhances immunotherapeutic responses.