CD19-CAR T-cell therapy induces deep tissue depletion of B cells in patients with autoimmune diseases (AIDs). This study demonstrates that CD19-CAR T-cell therapy, combined with standard lymphodepleting therapy, leads to complete B-cell depletion in secondary lymphoid tissues, such as lymph nodes, which has not been observed with antibody-based B-cell depletion therapies like rituximab (RTX). Sequential lymph node biopsies from patients with AIDs before and after CD19-CAR T-cell therapy showed complete depletion of CD19+ and CD20+ B cells in the lymph nodes, while RTX treatment did not achieve this. Additionally, non-lymphoid organs such as the colon, kidney, and gallbladder were completely depleted of B cells after CD19-CAR T-cell therapy. In contrast, RTX treatment left B cells in these tissues. The study also found that follicular structures and follicular dendritic cells (FDCs) were disrupted in the lymph nodes after CD19-CAR T-cell therapy, but not after RTX treatment. Plasma cells, T cells, and macrophages remained unchanged. The results suggest that CD19-CAR T-cell therapy induces a more profound B-cell depletion than RTX, which is important for understanding the biological effects of B-cell-targeted therapy in AIDs. The study highlights the importance of tissue analysis after B-cell depleting therapy to quantify the depth of treatment effect.CD19-CAR T-cell therapy induces deep tissue depletion of B cells in patients with autoimmune diseases (AIDs). This study demonstrates that CD19-CAR T-cell therapy, combined with standard lymphodepleting therapy, leads to complete B-cell depletion in secondary lymphoid tissues, such as lymph nodes, which has not been observed with antibody-based B-cell depletion therapies like rituximab (RTX). Sequential lymph node biopsies from patients with AIDs before and after CD19-CAR T-cell therapy showed complete depletion of CD19+ and CD20+ B cells in the lymph nodes, while RTX treatment did not achieve this. Additionally, non-lymphoid organs such as the colon, kidney, and gallbladder were completely depleted of B cells after CD19-CAR T-cell therapy. In contrast, RTX treatment left B cells in these tissues. The study also found that follicular structures and follicular dendritic cells (FDCs) were disrupted in the lymph nodes after CD19-CAR T-cell therapy, but not after RTX treatment. Plasma cells, T cells, and macrophages remained unchanged. The results suggest that CD19-CAR T-cell therapy induces a more profound B-cell depletion than RTX, which is important for understanding the biological effects of B-cell-targeted therapy in AIDs. The study highlights the importance of tissue analysis after B-cell depleting therapy to quantify the depth of treatment effect.