In this context, our findings raise the possibility that early downregulation of CD40 may constitute a transient compensatory mechanism that is ultimately lost during progression to CIS or relapsing-remitting MS, allowing for the unchecked formation of autoreactive B cell–T cell interactions and germinal center activity in peripheral lymphoid tissues or CNS-associated meningeal structures (39). This evidence concerns the gene CD40 and in situ carcinoma.