Single-cell landscape analysis unravels molecular programming of the human B cell compartment in chronic GVHD.
Single-cell landscape analysis unravels molecular programming of the human B cell compartment in chronic GVHD.
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DOI：
10.1172/jci.insight.169732
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发表时间：
2023-06-08
期刊：
影响因子：
8
通讯作者：
Sarantopoulos S
中科院分区：
文献类型：
--
作者：
Poe JC;Fang J;Zhang D;Lee MR;DiCioccio RA;Su H;Qin X;Zhang JY;Visentin J;Bracken SJ;Ho VT;Wang KS;Rose JJ;Pavletic SZ;Hakim FT;Jia W;Suthers AN;Curry-Chisolm IM;Horwitz ME;Rizzieri DA;McManigle WC;Chao NJ;Cardones AR;Xie J;Owzar K;Sarantopoulos S
Alloreactivity can drive autoimmune syndromes. After allogeneic hematopoietic stem cell transplantation (allo-HCT), chronic graft-versus-host disease (cGVHD), a B cell–associated autoimmune-like syndrome, commonly occurs. Because donor-derived B cells continually develop under selective pressure from host alloantigens, aberrant B cell receptor (BCR) activation and IgG production can emerge and contribute to cGVHD pathobiology. To better understand molecular programing of B cells in allo-HCT, we performed scRNA-Seq analysis on high numbers of purified B cells from patients. An unsupervised analysis revealed 10 clusters, distinguishable by signature genes for maturation, activation, and memory. Within the memory B cell compartment, we found striking transcriptional differences in allo-HCT patients compared with healthy or infected individuals, including potentially pathogenic atypical B cells (ABCs) that were expanded in active cGVHD. To identify intrinsic alterations in potentially pathological B cells, we interrogated all clusters for differentially expressed genes (DEGs) in active cGVHD versus patients who never had signs of immune tolerance loss (no cGVHD). Active cGVHD DEGs occurred in both naive and BCR-activated B cell clusters. Remarkably, some DEGs occurred across most clusters, suggesting common molecular programs that may promote B cell plasticity. Our study of human allo-HCT and cGVHD provides understanding of altered B cell memory during chronic alloantigen stimulation.
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DOI：
10.1084/jem.20092210
发表时间：
2010-05-10
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Allende ML;Tuymetova G;Lee BG;Bonifacino E;Wu YP;Proia RL
通讯作者：
Proia RL
影响因子：
4.4
作者：
Hauser, AE;Debes, GF;Manz, RA
通讯作者：
Manz, RA
影响因子：
13.6
作者：
Holla P;Dizon B;Ambegaonkar AA;Rogel N;Goldschmidt E;Boddapati AK;Sohn H;Sturdevant D;Austin JW;Kardava L;Yuesheng L;Liu P;Moir S;Pierce SK;Madi A
通讯作者：
Madi A
影响因子：
4.3
作者：
Greinix, Hildegard T.;Pohlreich, David;Pickl, Winfried F.
通讯作者：
Pickl, Winfried F.
DOI：
10.1073/pnas.1600557113
发表时间：
2016-04-05
影响因子：
11.1
作者：
Hodson, Daniel J.;Shaffer, Arthur L.;Staudt, Louis M.
通讯作者：
Staudt, Louis M.