CD22 Defines a Core Follicular Regulatory T Cell Subset that Controls the Antibody Response 2307652

Abstract

Abstract Introduction 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. Funding Source National Institutes of Health R01AI128976 Topic Categories Immune Response Regulation: Cellular Mechanisms (IRC)