Human B cells promote T-cell plasticity to optimize antibody response by inducing coexpression of T(H)1/T(FH) signatures.
J Allergy Clin Immunol
; 135(4): 1053-1060, 2015 Apr.
Article
en En
| MEDLINE
| ID: mdl-25258142
ABSTRACT
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 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.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 TH1 cytokine expression to support other cellular immune defenses.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Linfocitos B
/
Regulación de la Expresión Génica
/
Subgrupos de Linfocitos T
/
Transcriptoma
/
Formación de Anticuerpos
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Allergy Clin Immunol
Año:
2015
Tipo del documento:
Article
País de afiliación:
Países Bajos