CD154 CD40 AND CD70/CD27 INTERACTIONS HAVE DIFFERENT AND SEQUENTIAL FUNCTIONS IN T-CELL-DEPENDENT B-CELL RESPONSES - ENHANCEMENT OF PLASMA-CELL DIFFERENTIATION BY CD27 SIGNALING/

CD40, a TNF receptor family member, plays a central role in T cell-med iated B cell activation. We have recently demonstrated that CD27, anot her TNF receptor family member, was also involved in B cell regulation and enhanced Ig production. In this report we compare CD27 and CD40 s ignals in B cell function. We selectively mimicked the effect of T cel l help by addition to peripheral blood B cells activated with Staphylo coccus aureus Cowan I strain and IL-2 of irradiated 300-19 cells trans fected with either the CD70 (CD27 ligand) gene or the CD154 (CD40 liga nd) gene, the vector alone, or both CD70 and CD154 genes. CD27 ligatio n induced only a slight increase in B cell proliferation compared with the dramatic enhancement induced by CD40 ligation; double ligation pr oved to be less efficient than CD40 ligation alone. In contrast, IgG p roduction was increased only by CD27 ligation alone. Moreover, the CD2 7 signal was more efficient when it was given on day 2 of the culture rather than on day 0. Phenotypic analysis of the activated cells showe d that CD27 ligation increased the percentage of cells showing a plasm a cell profile (CD19(-), CD38(+)), whereas upon CD40 ligation most of the cells still had a germinal center-like phenotype (CD19(+), CD38(+) ). Our results suggest that the CD27 and CD40 signals are not synergis tic but, rather, are complementary and involve distinct steps of T cel l-dependent B cell activation. CD27 may be more important in the induc tion of plasma cell differentiation at a time when the expansion phase has already occurred.