Human B cells promote T-cell plasticity to optimize antibody response by inducing coexpression of TH1/TFH signatures
| Autor: | Ester B. M. Remmerswaal, M Makuch, Jacques Neefjes, Ineke J. M. ten Berge, Tineke Jorritsma, S. Marieke van Ham, Jelle de Wit, Hanny Klaasse Bos, Yuri Souwer |
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| Přispěvatelé: | Amsterdam institute for Infection and Immunity, Experimental Immunology, Cell Biology and Histology, Nephrology, Landsteiner Laboratory |
| Rok vydání: | 2015 |
| Předmět: |
Immunology
Priming (immunology) Biology Immunophenotyping Interferon-gamma Interleukin 21 T-Lymphocyte Subsets medicine Humans Immunology and Allergy Cytotoxic T cell IL-2 receptor Antigen-presenting cell B cell B-Lymphocytes Interleukins Cell Differentiation Natural killer T cell Acquired immune system Cell biology Phenotype medicine.anatomical_structure Gene Expression Regulation Antibody Formation Transcriptome Immunologic Memory |
| Zdroj: | Journal of allergy and clinical immunology, 135(4), 1053-1060. Mosby Inc. |
| ISSN: | 0091-6749 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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