(245) CD22 Defines a Core Follicular Regulatory T Cell Subset that Controls the Antibody Response

Introduction/Rationale: Germinal centers (GCs) formation and the associated antibody responses within B-cell follicles are dependent on the interaction of GC B cells with T Follicular Helper (TFH) and T Follicular Regulatory (TFR) cells. Follicular regulatory T (TFR) cells control antibody responses, yet the mechanisms underlying their differentiation and function remain incompletely understood.

Methods: We used flow cytometry to analyze the phenotype of TFR cells in both mouse and human samples. To investigate the role of CD22, we generated Treg cell-specific Cd22 knockout mice and assessed their antigen-specific immune responses following NP-OVA immunization. Furthermore, we performed in vitro co-culture assays to evaluate the suppressive function of TFR cells.

Results: We identified that both mouse and human TFR cells express CD22, representing a functionally distinct subset with a highly differentiated T follicular cell phenotype. Transcriptional analysis revealed that CD22+ TFR cells are enriched in a core T follicular cell gene signature distinct from their CD22– counterparts. Using a Treg cell-specific Cd22 deletion model, we observed dysregulated homeostatic and antigen-specific antibody responses, as well as age-dependent autoantibody production. Furthermore, CD22 deficiency impaired mTORC1-pSTAT3 activation, a pathway implicated in TFR cell function.

Conclusion: Our findings thus establish CD22 as critical to the differentiation of a core subset of TFR cells that regulates the magnitude and quality of the humoral immune response.