Sex-Based Differences in Thyroid Plasma B Cell Infiltration: Implications for Autoimmune Disease Susceptibility

Abstract

Thyroid autoimmune diseases, such as Hashimoto thyroiditis and Graves disease, are significantly more prevalent in women than in men, suggesting underlying biological differences in immune system function and regulation between sexes. Plasma B cells are crucial in autoimmunity due to their role in producing antibodies targeting self-antigens, but their presence in the thyroids of women without clinical autoimmune diseases remains largely unexplored. This study investigates the infiltration of plasma B cells in female thyroids specifically excluding those with any clinical signs of autoimmune diseases. Using bulk RNA-seq analysis, we identified significant sex differences in gene expression profiles, particularly in genes associated with plasma B cells. Single-cell RNA-seq and spatial transcriptomic analyses further revealed that the CXCL13-CXCR5 signaling axis plays a pivotal role in recruiting and organizing plasma B cells within the thyroid tissue. These findings suggest that the inherent presence of plasma B cells in the female thyroid, driven by CXCL13, may contribute to the higher risk of developing autoimmune thyroid diseases in women. Our study provides new insights into the immune landscape of the thyroid and underscores the importance of understanding sex-specific differences in immune cell distribution and function.