Comparative In Vitro Immune Stimulation Analysis of Primary Human B Cells and B Cell Lines

Table 2

Characterization of pharmacological inhibitors in phenotypic assays.

Chemical	Target	PBMC	Primary B cell	Namalwa
		MLR	IgG production	Viability WST-1	CD40	CD69	CD70	CD80	CD83	CD86
Bortezomib	Proteasome: 30–100	35	90	10	—	—	—	—	—	—
Ibrutinib	BTK: 0.5	4 000	<1	1 800	690		670	>	730	<30
Chloroquine	TLR 3, 7, 8, and 9: 560	>	95	>	70	90	1 000	60	210	<30
Dasatinib	SRC: 0.55; BCR/ABL: 3; LYN: 8.5; Other TK	15	55	20	—	—	—	—	—	—
LY-294,002 hydrochloride	PI3K: 3 000	5 100	670	4 600	2 800	>	2 500	2 200	>	450
MK-2206 2HCl	AKT1/2/3: 8/12/65	3 500	25	2 700	1 500		1 200	1 100	120	<30
AZD-5363	AKT1/2/3: 3/7/7	2 600	600	3 000	1 500		850	>	2 200	<30
TPCA-1	IKK-2: 17.9; IKK-1: 400	360	450	2 800	210	550	480	700	550	<30
STAT3 inhibitor VII	STAT3: 170	8 500	>	>	>	>	>	2 800	>	1 000
SAHA	Class I & II histone deacetylase (HDAC): <86; HDAC1: 13.7	5 000	440	2 100	>		>	1 300	>	>
Mirin	Mre11-Rad50-Nbs1 (MRN) complex (DNA-repair); Cell-free: 12 000; Human: 66 000	>	1 400	>	>	>	>	>	>	>

The table shows the IC₅₀ (nM) of the inhibitors on the molecular target and in the different phenotypic assays: MLR with human PBMCs, IgG production by human B cell stimulated by ODN2006, and surface markers expression on ODN2006-stimulated Namalwa. Cytotoxic counterscreen (WST-1) was performed on Namalwa cells. : indicates an increase in expression.