Using blood samples from autologous BMT‐ and natalizumab‐treated MS patients, we demonstrate that high B‐cell EBV load associates with the development of CXCR3+ class‐switched B cells (ex vivo) and plasma cells under IL‐21‐, CD40L‐ and IFN‐γ‐inducing conditions (in vitro). Here, CD40LG is linked to myeloid sarcoma.