Human B cells promote T-cell plasticity to optimize antibody response by inducing coexpression of TH1/TFH signatures

Background B cells mediate humoral immunity against pathogens but also direct CD4 + T-cell responses. Recent plasticity studies in mice have challenged the concept of strict fate commitment during CD4 + T-cell differentiation into distinct subsets. Objective We sought to elucidate the contribution of human antigen-primed B cells in CD4 + T-cell responses that support humoral immunity. Methods CD4 + T-cell differentiation by primary human B cells was investigated in in vitro cocultures by using tetanus toxoid and Salmonella species as antigen models. T-cell differentiation was assessed by using intracellular cytokines and subset-specific transcription factors and markers. IgM and IgG formation was analyzed by means of ELISA. Results Human B cells, but not dendritic cells, induce prominent and stable coexpression of T H 1 and follicular helper T (T FH ) cell characteristics during priming and on antigen recall. T H 1/T FH cells coexpress the T H 1 and T FH effector cytokines IFN-γ and IL-21 and the T FH marker CXCR5, demonstrating that the coexpressed T H 1 and T FH subset–specifying transcription factors T-box transcription factor (T-bet) and B cell lymphoma 6 are both functionally active. B cell–derived IL-6 and IL-12 controlled respective expression of IL-21 and IFN-γ, with IL-21 being key for humoral immunity. Conclusion Human B cells exploit CD4 + T-cell plasticity to create flexibility in the effector T-cell response. Induction of a T-cell subset coexpressing IL-21 and IFN-γ might combine IL-21–mediated T-cell aid for antibody production while maintaining T H 1 cytokine expression to support other cellular immune defenses.