Follicular Helper T Cells in Systemic Lupus Erythematosus: Why Should They Be Considered as Interesting Therapeutic Targets?

Table 3

Function of -related molecules during B cell help, maintenance, and regulation.

T cell molecule	Ligand	Function in mice	Function in humans
CD40L	CD40	The formation of GC and the generation of mem B cells is inhibited in the absence of CD40L [138]	CD40-CD40L interaction is required for the survival of GC B cells [71]
ICOS	ICOSL	are lost in the absence of B cells [12]	Patients with LOF mutation in ICOS have reduced numbers of mem B cells [133]
CD28	CD80	CD80 expression on follicular B cells and its interaction with CD28 on T cells is essential for maintenance of the phenotype [139]	ND
IL-21	IL-21R	IL-21 promotes the differentiation of B cells to mem B cells and PC [52]; Mem B cells and PC fail to expand following immunization in IL21^−/− mice [35]	B cell differentiation by tonsillar CXCR5^+ T cells is mediated by IL-21 [140]
IL-4	IL-4R	GC cells produce IL-4, which is required for optimal B cell help [141, 142]	ND
BAFF	BR3/TACI/BCMA	TACI^−/− mice have reduced numbers of PC due to a failure in downregulating Bim [36]; GC produce BAFF and T-cell restricted BAFF deficiency impairs affinity maturation [37]	ND
PD-1	PD-L1/PD-L2	GC B cell survival is decreased in the absence of PD-1 [143]	CXCR5^+PD-1 T cells promote antibody responses [67]
BTLA	HVEM	Numbers of IL-21-producing -like cells are increased in BTLA^−/− mice [39]	ND
SAP	SLAM	IL-4 production by SLAM^−/− cells is markedly reduced [142]	ND

GC: germinal center; ND: not determined; LOF: loss of function; mem B cells: memory B cells; PC: plasma cells.