While studying the plasma cell (PC) compartment in human tonsils, we identified that immunoglobulin kappa or lambda chain‐expressing PCs are the main cells expressing granzyme B (GrzB). In vitro studies revealed that activated B cells differentiated into GrzB‐expressing PCs when co‐cultured with macrophages and follicular helper T cells. This effect could be reproduced on combined stimulation of IL‐15 (produced by macrophages) and IL‐21 (produced by T follicular helper cells) in a STAT3‐dependent manner. Whereas IL‐21 triggers the transcription of mRNA of GrzB, IL‐15 synergizes the translation of GrzB proteins. The precise role of GrzB in PC biology remains to be understood and studies in mice will not help as their PCs do not express GrzB.