The molecules of the TNF superfamily and their receptors play crucial roles in the humoral immune response. In view of the powerful effects on germinal center (GC) B cell differentiation, the expression of these molecules should be tightly regulated. In this study, we have undertaken a detailed analysis of the regulation of CD27 expression following the differentiation of GC B cells supported by a follicular dendritic cell line. We show that CD27 is differentially expressed on B cell subpopulations at different stages of differentiation. Naive B cells are virtually negative but plasma cells generated in vivo are strongly positive for CD27 expression. GC B cells that exhibit a moderate expression of CD27 remarkably up‐regulate the expression levels of this molecule when they differentiate into plasma cells, which is induced by IL‐10. The up‐regulation of CD27 expression correlates with that of CD38. Therefore, high expression of CD27 molecules emerges as a specific marker for plasma cells. Our results suggest an important role for CD27 in the differentiation of GC B cells into plasma cells. Evaluation of CD27 expression levels may be of a clinical significance in assessment of B cell maturation in immunocompromised patients.