Adapting to the world: The determination and plasticity of T follicular helper cells

Antibodies are crucial in host defenses as well as in allergic diseases. T follicular helper (T_FH) cells play essential roles in germinal center reactions by facilitating B-cell differentiation and immunoglobulin affinity maturation and isotype switching. Although T_FH cells have a unique gene transcription program and regulatory network, recently there has been increasing evidence of T_FH cell plasticity, with some T_FH cells expressing genes typically related to other types of effector T cells associated with different types of Ig subclasses and in the context of different pathogen infections and health conditions. Here, we review the plasticity of T_FH cells in various types of immune responses. We also point out the important implications of T_FH plasticity in understanding and treating human diseases, including allergy.