 An additional TH subset called follicular helper T Tfh cells has recently been identified in germinal centers and also in whole blood circulating Tfh cells. These cells regulate B-cell maturation and immunoglobulin production during normal immune responses. They produce factors essential for B cell selection and maturation into memory B-cells or long-lived antibody-secreting plasma cells. Furthermore, they also seem to favor pathogenic autoantibody production in systemic autoimmunity, and therefore could potentially represent a novel therapeutic target in autoimmune diseases. Indeed, rheumatoid arthritis synovium is characterized by the presence of ectopic lymphoid structures, resembling germinal centers. Potentially, Tfh cells from these nonlymphoid tissues could promote B-cell maturation and synthesis of pathogenic autoantibody production, thus potentiating tissue injury. Interestingly, production of IL-21 by Tfh cells is implicated in B cell activation, and the same cytokine have been associated with rheumatoid arthritis RA pathogenesis. 