The ion transporter Na+-K+-ATPase enables pathological B cell survival in the kidney microenvironment of lupus nephritis

The kidney is a comparatively hostile microenvironment characterized by highsodium concentrations; however, lymphocytes infiltrate and survive therein in autoimmune diseases such as lupus. The effects of sodium-lym-phocyte interactions on tissue injury in autoimmune diseases and the mechanisms used by infiltrating lympho-cytes to survive the highsodium environment of the kidney are not known. Here, we show that kidney-infiltrating B cells in lupus adapt to elevated sodium concentrations and that expression of sodium potassium adenosine triphosphatase (Na+-K+-ATPase) correlates with the ability of infiltrating cells to survive. Pharmaco-logical inhibition of Na+-K+-ATPase and genetic knockout of Na+-K+-ATPase gamma subunit resulted in reduced B cell infiltration into kidneys and amelioration of proteinuria. B cells in human lupus nephritis biopsies also had high expression of Na+-K+-ATPase. Our study reveals that kidney-infiltrating B cells in lupus initiate a tissue adaption program in response to sodium stress and identifies Na+-K+-ATPase as an organ-specific therapeutic target.