Tonsil Human Atlas

Definitions

Note: italic words indicate genes; uppercase words with + or - indicate surface protein.

1. Antigen presenting cells (APC) <—- antigen —> Follicular Dendritic Cell (FDC)

2. CD4 T follicular and non-follicular cell fate decision

CD4 T follicular helper cell (Tfh) differentiation:

• BCL6 is the master transcription factor.
• PRDM1 is absent.

Tfh specification

1. Beginning: naive CD4 T cells are activated by antigen-presenting DCs. Naive CD4 T cell markers: LEF1, CCR7, CD62L+, CD45RA+.
2. CD4 T cells differentiate into central memory (CM) CD4 T cells. This state has decreased CCR7 expression and is CD45RO+, CD127+.

Central memory CD4 T cells split into two subpopulations:

• CM pre-Tfh cells: increased follicular marker genes.
• CM pre-non-Tfh cells: increased ANXA1, S100A4, and ITGB1 (CM markers).

Activation by DCs upregulates BCL6, which induces CXCR5 (chemokine receptor), represses CCR7, and supports migration of pre-Tfh cells to the border of B cell follicles.

Tfh-lightzone-GC (Tfh-LZ-GC) upregulates IL21, an inducer for early GC Tfh differentiation.