IL-1β and IL-6 synergistically drive murine TFH cell differentiation and maintenance in vitro

T follicular helper (TFH) cells are critical in supporting B-cell responses, which ultimately establish long-term protective immunity against infection and some cancers by producing protective B cells, including antibody-secreting cells and memory cells. However, this same GC output can also promote autoimmune pathology. Therefore, TFH cells are at the core of humoral immunity, underscoring TFH cells as targets for long-term protective and/or pathologic immune responses. Here we define conditions that promote physiologically relevant TFH cell differentiation in vitro. We demonstrate that in addition to T-cell receptor (TCR) signaling, IL-6 and IL-1β individually and jointly promote TFH cell differentiation. These findings highlight key requirements for generating functional TFH cells, providing a model to study therapeutic impacts on TFH cells across diverse disease settings.