# Germinal center formation is resilient to CD69 deletion on T follicular helper cells

## TL;DR

This study shows that CD69 is not essential for T follicular helper cells to support B-cell responses in germinal centers.

## Contribution

The study reveals that CD69 is not required for TFH cell function or germinal center formation in mice.

## Key findings

- Genetic deletion of CD69 on TFH cells did not impair germinal center formation or B-cell responses.
- Memory B cells and plasma cells were generated at normal frequencies in CD69-deficient TFH cells.
- Secondary immunization showed no disruption in germinal center responses despite CD69 deletion.

## Abstract

T follicular helper (TFH) cells are a helper T‐cell subset that is defined by their localisation to B‐cell areas of secondary lymphoid tissues, enabling them to provide their B‐cell helper function. Precursors of TFH cells migrate to the B‐cell follicles by upregulating CXCR5 and downregulating CCR7, a process that can be blocked by S1PR1 overexpression. TFH cells and their precursors also express the early activation antigen CD69, which is a negative regulator of S1PR1. In this study, we tested the hypothesis that CD69 expression by TFH cells is important for their differentiation and localisation after immunization. Genetic deletion of CD69 on TFH cells and a proportion of their precursors did not alter their formation, nor their ability to support high‐affinity B‐cell responses. This demonstrates that although CD69 is expressed highly on TFH cells, it is not necessary for their formation or their B‐cell helper functions in lymph nodes (LNs).

CD69 is upregulated on human and mouse CD4+ T follicular helper (TFH) cells within the germinal center. In this article, we use an Il21‐cre mouse strain to ablate floxed Cd69 genes from TFH cells and a proportion of their precursors. We find that when TFH cells lack CD69, the germinal center response remains intact, supporting B‐cell affinity maturation and the generation of memory B cells (MBCs) and plasma cells at normal frequencies. Following secondary immunization, the germinal center response remained unperturbed, demonstrating that the germinal center is resilient to deletion of CD69 from TFH cells.