Co-ligation of CD44 on naive human tonsillar B cells induces progression towards a germinal center phenotype.

The precise signaling pathways to induce a germinal center (GC) phenotype and somatic mutations in human B cells are presently not understood. Major phenotypical hallmarks of a human GC B cell are up-regulated expression of CD10 and CD95 together with a heterogeneous expression of CD77. Activation of resting human tonsillar B cells using anti-CD40 and anti-IgM antibodies normally only induces up-regulation of CD38 and CD71 but has no effect on the typical GC markers. However, we show here that an additional co-ligation of the glycoprotein CD44 on such tonsillar B cells up-regulated the typical human GC markers CD10, CD38, CD77 and CD95, and down-regulated CD24 and CD39 as well as induced progression towards apoptosis in these cells; all characteristics of GC B cells. These data indicate a functional role of CD44 during activation of human naive B lymphocytes and in the generation of GC B cells.