Herein, we showed that B lymphocyte depletion in BALB/c mice completely abolished anti‐STEC O157:H7‐specific Ab production and these mice die due to STEC O157:H7 infection with high levels of urea, neutrophilia, and significant weight loss, all of which are hallmarks of renal damage and Stx2‐associated HUS. This evidence concerns the gene STX2 and hemolytic-uremic syndrome.