Distinct roles of ICOS and CD40L in human T-B cell adhesion and antibody production

被引:20
作者
Liu, Zhicui [1 ,2 ]
Liu, Shuai [2 ]
Zhang, Yan [3 ]
Zeng, Weihong [4 ]
Wang, Shujun [2 ]
Ji, Ping [2 ]
Pan, Meng [5 ]
Zhu, Cheng [6 ]
Wang, Ying [2 ]
机构
[1] Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Dept Dermatol, Shanghai 200072, Peoples R China
[2] Shanghai Jiao Tong Univ, Sch Med, Shanghai Inst Immunol, Dept Immunol & Microbiol, Shanghai 200025, Peoples R China
[3] Navy Mil Med Univ, Inst Biomed Engn, Shanghai 200433, Peoples R China
[4] Shanghai Jiao Tong Univ, Sch Med, Int Peace Matern & Child Hlth Hosp, Inst Embryo Fetal Original Adult Dis, Shanghai 200030, Peoples R China
[5] Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Dept Dermatol, Shanghai 200025, Peoples R China
[6] Georgia Inst Technol, Wallace H Coulter Dept Biomed Engn, Atlanta, GA 30332 USA
基金
中国国家自然科学基金;
关键词
Inducible co-stimulatory molecule (ICOS); CD40L; Cell adhesion; IgG; IgM production; Systemic lupus erythematosus; SYSTEMIC-LUPUS-ERYTHEMATOSUS; LIGAND BINDING-KINETICS; MOLECULE ICOS; ANTIGEN; ACTIVATION; TCR; COSTIMULATION; PYK2; RECOGNITION; MECHANISM;
D O I
10.1016/j.cellimm.2021.104420
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
CD40-CD40L and inducible co-stimulatory molecule (ICOS)-ICOSL ligations are demonstrated to play critical roles in CD4+ T-B interaction for B cell activation and differentiation in mouse models. Herein, by using a micropipette adhesion assay and an in vitro CD4+ T-B cell coculture system simultaneously, we intended to dissect their roles in human CD4+ T-B adhesion and IgG/IgM production. With the upregulation of CD40L and ICOS expressions on CD4+ T cells upon TCR/CD28 stimulation in vitro, activated CD4+ T cells exhibited enhanced adhesion with autologous B cells at a single cell level when compared to the resting counterparts. Blockade of ICOS dramatically damped the adhesion between CD4+ T and B cells whereas less effect of CD40L blockade was observed. On the contrary, blockade of CD40L led to the dramatic decrease in IgG/IgM production when B cells were cocultured with activated CD4+ T cells together with the decrease in the induction of CD19hi B cells. However, ICOS blockade displayed less attenuation on IgG/IgM production. Distinct roles of CD40-CD40L and ICOS-ICOSL in cell adhesion and IgG/IgM production were also observed in CD4+ T-B cell interaction in system lupus erythematosus patients. The blockade of CD40L, rather than ICOS, led to the dramatic decrease in the phosphorylation of Pyk2 in CD19hi B cells and total B cells. Our study thus provides the evidence that CD40L and ICOS on activated CD4+ T cells either upon in vitro activation or at the pathogenic state function diversely during CD4+ T-B cell interactions. While ICOS-ICOSL ligation is more likely to be engaged in cell adhesion, CD40-CD40L provides indispensable signal for B cell differentiation and IgG/IgM production. Our results are thus indicative for the segregating costimulation of CD40-CD40L and ICOS-ICOSL on CD4+ T cells for B cell activation and differentiation, which might be helpful for the dissection of SLE pathogenesis.
引用
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页数:9
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