Efficient Expansion of Human Granzyme B–Expressing B Cells with Potent Regulatory Properties

• DOI: 10.4049/jimmunol.2000335
• Publication Date: 2020-09-18T20:21:16Z
• Authors: Mélanie Chesneau; Hoa Le Mai; Richard Danger; Sabine Le Bot; Thi-Van-Ha Nguyen; Josselin Bernard; Cyrielle Poullaouec; Pierrick Guerrif; Sophie Conchon; Magali Giral; Béatrice Charreau; Nicolas Degauque; Sophie Brouard
• Keywords: Regulatory B cells

Granzyme B-expressing B cells have been shown to be an important regulatory cell subset in humans. However, it is unclear which subpopulations of express GZMB under normal conditions and protocols effectively induce ex vivo expansion GZMB+ cells. We found that the peripheral blood individuals, plasmablasts were major subpopulation expressed GZMB. when using vitro plasmablast differentiation protocol, we obtained only 2% Nevertheless, mixture containing IL-21, anti-BCR, CpG oligodeoxynucleotide, CD40L, IL-2, able obtain more than 90% after 3 d culture. through this protocol suppressed proliferation autologous allogenic CD4+CD25- effector T The suppressive effect was partially dependent totally contact but not associated with increase apoptosis or uptake by Interestingly, showed produced promoted ERK1/2-dependent manner, facilitating expansion. tended undergo prolonged stimulation, may considered a negative feedback mechanism limit their uncontrolled Finally, expanded exhibited phenotype enriched CD307bhi, CD258hiCD72hi, CD21loPD-1hi subpopulations. Our study, our knowledge, provides new insight into biology efficient method expand for future therapy applications.