Interleukin (IL)-21 is a key regulator of T follicular helper (Tfh) cell development in germinal centers and represents a major cytokine secreted by Tfh cells that critically regulates the differentiation of memory B cells and plasma cells. Interestingly, high production of IL-21 has been detected in populations of Tfh and Tfh-like cells that are external to germinal centers, and these cells can also regulate B cell activation and Ig production. This study showed that a population known as T peripheral helper (Tph) cells, comprising 30% of synovial fluid CD4+ T cells in rheumatoid arthritis patients, expresses chemokine receptors (CCR2, CX3CR1, CCR5) that allow the cells to migrate to sites of inflammation. In contrast to Tfh cells localized in germinal centers, Tph cells are programmed cell death 1 (PD-1)hi but are not exhausted, and they express high levels of B lymphocyte-induced maturation protein 1 (BLIMP1) but low levels of B cell lymphoma protein 6 (BCL6). Moreover, Tph and Tfh cells have not been interconverted in vitro, suggesting that Tph cells develop in vivo to induce B cell responses in pathological situations, such as within inflamed synovium. This Recommendation is of an article referenced in an F1000 Faculty Review also written by Rosanne Spolski, Daniel Gromer, and Warren J. Leonard.