Phenotype and function of human B cells expressing CD70 (CD27 ligand)

Abstract

CD70, the cellular ligand of the tumor necrosis factor receptor family member CD27, can be found on a limited number of germinal center (GC) B cells in some tonsils, on scattered lymphocytes residing in secondary lymphoid organs, and on a fraction of the circulating B cell population. Due to the restricted expression of CD70 in vivo, we analyzed signals that determine CD70 expression levels and characterized the phenotype and function of CD70⁺ B cells. Expression of CD70 on B cells activated in vitro was found to be dependent on the continuous presence of a B cell antigen receptor cross‐linking agent, and induced or potentiated by CD40 ligation but was down‐modulated by the Th2 cytokines interleukin (IL)‐4 and IL‐13. Both in peripheral blood and tonsil cell suspensions, CD70⁺ B cell subpopulations were found to be enriched for CD27‐and IgG‐expressing cells, but contained less IgD⁺ B cells. Additional analysis of markers which define specific differentiation stages (Bm1‐5) of mature B cells within human tonsils did not place CD70‐expressing B cells in one of these subsets. Functional experiments revealed that whereas both CD70⁻ and CD70⁺ B cells can secrete immunoglobulin after activation with a combination of Staphylococcus aureus Cowan strain I and IL‐2, only CD70⁺ B cells can produce large quantities of antibodies when stimulated in a T cell‐dependent fashion. Our combined data imply that CD70 is a marker for mature B cells which have recently been primed by antigen in vivo.