Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Jul 7;18(1):36.
doi: 10.1186/s12865-017-0216-x.

γδTFH cells promote B cell maturation and antibody production in neuroblastoma

Wenjun Mou  1   2 , Wei Han  3 , Xiaoli Ma  4 , Xiaolin Wang  1   2 , Hong Qin  3 , Wen Zhao  4 , Xiaoya Ren  1   2 , Xi Chen  1   2 , Wei Yang  3 , Haiyan Cheng  3 , Xisi Wang  4 , Hui Zhang  1   2 , Xin Ni  5 , Huanmin Wang  6 , Jingang Gui  7   8
Affiliations

γδTFH cells promote B cell maturation and antibody production in neuroblastoma

Wenjun Mou et al. BMC Immunol. .

Abstract

Background: Previous studies have shown that γδ TFH cells are capable of modulating antibody production in immunized and infected mouse model. In recent studies, human γδ TFH cells are shown to contribute to the activation of humoral immunity and promote the maturation of B cells. However, little information is available on their involvement in neuroblastoma (NB) pathogenesis.

Results: In the present study, the frequency of γδ TFH cells in 74 NB patients was significantly higher compared with that in 60 healthy controls. Moreover, most γδ TFH cells in NB patients had a naive phenotype with up-regulation of CD25, CD69, HLA-DR and CD40L and down-regulation of ICOS. Importantly, γδ TFH cells in NB patients produced more IL-4 and IL-10 than those in healthy controls. Furthermore, serum total IgG level was significantly increased in NB patients compared with healthy controls. The expression of CD23 on B cells was up-regulated while CD80 expression was significantly down-regulated in NB patients. Further analysis of B cell compartment showed that the frequency of CD19+CD27hi plasma cells was enhanced in NB patients. Spearman's correlation analysis revealed that the frequency of γδ TFH cells was positively correlated to serum total IgG level and CD19+CD27hi plasma cells in NB patients, but negatively correlated to CD19+ B cells.

Conclusions: We concluded that γδ TFH cells might promote B cell maturation and antibody production in NB patients.

Keywords: B cells; CXCR5; Interleukin 10; Interleukin 4; Neuroblastoma; γδT cells.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Circulating CXCR5+ γδT cells were significantly increased in NB patients. a The percentage of γδT cells in peripheral blood from NB patients (n = 74), other blastoma patients (n = 19) and healthy controls (n = 60) were analyzed by flow cytometry. b The percentage of CXCR5+ cells in γδT cells from NB patients (n = 65), other blastoma patients (n = 13) and healthy controls (n = 19) were analyzed by flow cytometry. Each dot represents one individual. *P < 0.05. **P < 0.01, ***P < 0.001, ns = not significantly different
Fig. 2
Fig. 2
Surface phenotype of γδ TFH cells in NB patients. a The percentage of CD45RA, CD45RO, CD62L and CCR7 in CXCR5+ γδT cells and CXCR5− γδT cells from NB patients were shown. b The percentage of CD25, CD69, HLA-DR and CD40L in CXCR5+ γδT cells and CXCR5− γδT cells from NB patients were shown. c The percentage of ICOS in CXCR5+ γδT cells and CXCR5− γδT cells from NB patients were shown. Each dot represents one individual. *P < 0.05. **P < 0.01, ***P < 0.001
Fig. 3
Fig. 3
γδ TFH cells secreted IL-4 and IL10 was increased in NB patients. a Intracellular staining of IL-4 in CXCR5+ γδT cells in NB patients (n = 15) and health controls (n = 14). b Intracellular staining of IL-10 in CXCR5+ γδT cells in NB patients (n = 15) and health controls (n = 15). c Serum level of IL-4 were measured by Luminex Multiplex assay in NB patients (n = 35) and health controls (n = 25). d Serum level of IL-10 were measured by Luminex Multiplex assay in NB patients (n = 35) and health controls (n = 25). e Intracellular staining of IFNγ in CXCR5+ γδT cells in NB patients (n = 10) and health controls (n = 9). f Intracellular staining of IL-2 in CXCR5+ γδT cells in NB patients (n = 8) and health controls (n = 8). Each dot represents one individual. *P < 0.05. ***P < 0.001, ns = not significantly different
Fig. 4
Fig. 4
Antibody production and B-cell phenotype in NB patients. a Total serum level of IgG, IgA and IgM were measured by ELISA in NB patients (n = 43) and health controls (n = 52). Each dot represents one individual. *P < 0.05, ns = not significantly different. b The percentage of CD3−CD19+ B cells in peripheral blood from NB patients (n = 39) and health control (n = 50) were analyzed by flow cytometry. Each dot represents one individual. *P < 0.05. c Phenotype analysis of CD3−CD19+ B cells. Data were expressed as the mean + SEM. *P < 0.5, **P < 0.01, ns = not significantly different d The percentage of IgD+CD27−, CD27+ and CD19+CD27hi B cells in peripheral blood from NB patients and health control were shown. Each dot represents one individual. **P < 0.01, ns = not significantly different. d Phenotype analysis of CD3−CD19+ B cells. Data were expressed as the mean + SEM. **P < 0.01, ns = not significantly different
Fig. 5
Fig. 5
The frequency of γδ TFH cells is positively correlated to the serum total IgG level and CD19+CD27hi plasma cells in NB patients. a Correlation of CXCR5+ γδT cells with CD19+ B cells, serum total IgG level or CD19+CD27hi plasma cells in NB patients. Each dot represents one individual. b Correlation of CXCR5+ γδT cells with CD19+ B cells, serum total IgG level or CD19+CD27hi plasma cells in healthy control. Each dot represents one individual. c Correlation of CXCR5+ γδT cells with serum total IgA level or serum total IgM level in NB patients. Each dot represents one individual
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Eivazi S, Bagheri S, Hashemzadeh MS, Ghalavand M, Qamsari ES, Dorostkar R et al. Development of T follicular helper cells and their role in disease and immune system. Biomed Pharmacother. 2016. doi:10.1016/j.biopha.2016.10.083. - PubMed
    1. Brandes M, Willimann K, Lang AB, Nam KH, Jin C, Brenner MB, et al. Flexible migration program regulates gamma delta T-cell involvement in humoral immunity. Blood. 2003;102(10):3693–3701. doi: 10.1182/blood-2003-04-1016. - DOI - PubMed
    1. Constant P, Davodeau F, Peyrat MA, Poquet Y, Puzo G, Bonneville M, et al. Stimulation of human gamma delta T cells by nonpeptidic mycobacterial ligands. Science. 1994;264(5156):267–270. doi: 10.1126/science.8146660. - DOI - PubMed
    1. Zheng J, Orentas R, Yan X, Liu H. Humoral immune response induced by an engineered cell-based neuroblastoma vaccine with or without CD25 blockade. Acta Biochim Biophys Sin. 2011;43(2):124–132. doi: 10.1093/abbs/gmq123. - DOI - PubMed
    1. Wen L, Hayday AC. Gamma delta T-cell help in responses to pathogens and in the development of systemic autoimmunity. Immunol Res. 1997;16(3):229–241. doi: 10.1007/BF02786392. - DOI - PubMed

Publication types