Abstract
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. We sought to elucidate the contribution of human antigen-primed B cells in CD4(+) T-cell responses that support humoral immunity. 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. Human B cells, but not dendritic cells, induce prominent and stable coexpression of TH1 and follicular helper T (TFH) cell characteristics during priming and on antigen recall. TH1/TFH cells coexpress the TH1 and TFH effector cytokines IFN-γ and IL-21 and the TFH marker CXCR5, demonstrating that the coexpressed TH1 and TFH 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. 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 TH1 cytokine expression to support other cellular immune defenses
Original language | English |
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Pages (from-to) | 1053-1060 |
Number of pages | 8 |
Journal | Journal of allergy and clinical immunology |
Volume | 135 |
Issue number | 4 |
DOIs | |
Publication status | Published - Apr 2015 |
Keywords
- Antibody Formation
- B-Lymphocytes/immunology
- Cell Differentiation
- Gene Expression Regulation
- Humans
- Immunologic Memory
- Immunophenotyping
- Interferon-gamma/metabolism
- Interleukins/metabolism
- Phenotype
- T-Lymphocyte Subsets/cytology
- Transcriptome