Since TCR signaling is the most significant upstream regulator of transcriptomic changes in CXCR4-expressing memory CD4+ T cells (Fig. 4C), the quantitative increase in HLA-DR expression on B cells could contribute to the increased CXCR4 expression observed on memory CD4+ T cells in RA, and the increased amount of serum IL-21 might also play a role (Fig. 3B and Figure S4B). Here, CD4 is linked to rheumatoid arthritis.