Authors: Orecchioni, M; Fusco, L; Mall, R; Bordoni, V; Fuoco, C; Rinchai, D; Guo, S; Sainz, R; Zoccheddu, M; Gurcan, C; Yilmazer, A; Zavan, B; Menard-Moyon, C; Bianco, A; Hendrickx, W; Bedognetti, D; Delogu, LG

Article; Early Access.
Nanoscale. vol: . page: 2040-3364.
Date: . .
Doi: 10.1039/d1nr04355b.

Abstract:
We recently found by single-cell mass cytometry that ex vivo human B cells internalize graphene oxide (GO). The functional impact of such uptake on B cells remains unexplored. Here, we disclosed the effects of GO and amino-functionalized GO (GONH(2)) interacting with human B cells in vitro and ex vivo at the protein and gene expression levels. Moreover, our study considered three different subpopulations of B cells and their functionality in terms of: (i) cytokine production, (ii) activation markers, (iii) killing activity towards cancer cells. Single-cell mass cytometry screening revealed the higher impact of GO on cell viability towards naive, memory, and plasma B cell subsets. Different cytokines such as granzyme B (GrB) and activation markers, like CD69, CD80, CD138, and CD38, were differently regulated by GONH(2) compared to GO, supporting possible diverse B cell activation paths. Moreover, co-culture experiments also suggest the functional ability of both GOs to activate B cells and therefore enhance the toxicity towards HeLa cancer cell line. Complete transcriptomic analysis on a B cell line highlighted the distinctive GO and GONH(2) elicited responses, inducing pathways such as B cell receptor and CD40 signaling pathways, key players for GrB secretion. B cells were regularly left behind the scenes in graphene biological studies; our results may open new horizons in the development of GO-based immune-modulatory strategies having B cell as main actors..