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pre-GC and GC B cell scRNAseq

Alternate Titles(s): Distinct Metabolic Requirements Regulate B Cell Activation and Germinal Center Responses

UID: 10907

Author(s): Smolkin, Ryan*, Sharma, Rahul*, Chaudhuri, Jayanta* * MSK affiliated

Description
Summary from GEO:

"Following infection or vaccination, activated B cells at extrafollicular sites or within germinal centers (GCs) undergo vigorous clonal proliferation. Proliferating lymphocytes have been shown to undertake lactate dehydrogenase A (LDHA)-dependent aerobic glycolysis; however, the specific role of this metabolic pathway in a B cell transitioning from a naïve to a highly proliferative, activated state remains poorly defined. Here, we deleted LDHA in a stage- and cell-specific manner. We find that ablation of LDHA in a naïve B cell did not profoundly affect its ability to undergo a T cell-independent extrafollicular B cell response. On the other hand, LDHA-deleted naïve B cells had a severe defect in the capacities to form GCs and mount GC-dependent antibody responses. In addition, loss of LDHA in T cells severely compromised B cell-dependent immune responses. Strikingly, when LDHA was deleted in activated, as opposed to naïve, B cells, there were only minimal effects on the GC reaction and in the generation of high-affinity antibodies. These findings strongly suggest that naïve and activated B cells have distinct metabolic requirements that are further regulated by niche and cellular interactions."

Overall design from GEO:

"We performed scRNA sequencing to understand role of LDHA in the activation and proliferation of germinal center (GC) B cells. We combined this technology to HASH-sequencing in order to measure analyze LDHA-sufficient and -deficient GCs in triplicate and BCR sequencing to detect clonality and validate hypermutation in the early potential GC cells."
Subject of Study
Mus musculus
Subject(s)
B-Lymphocytes
Germinal Center
Lactate Dehydrogenases
Lymphocyte Activation
Single-Cell Gene Expression Analysis
T-Lymphocytes
Access via GEO


Accession #: GSE232659

Access via BioProject


Accession #: PRJNA973113

Access Restrictions
Free to All
Access Instructions
The NCBI Gene Expression Omnibus and BioProject databases provides open access to these files.
Associated Publications
Sharma R, Smolkin R, Chowdhury P, Fernandez K, Kim Y, Cols M, Alread W, Yen W, Hu W, Wang Z, Violante S, Chaligné R, Li M, Cross J, Chaudhuri J. Distinct metabolic requirements regulate B cell activation and germinal center responses. Nature Immunology. 2023; 24(8):1358-1369.
Equipment Used
Illumina NovaSeq 6000
Dataset Format(s)
TSV, TAR, MTX
Dataset Size
22.6 MB
Data Catalog Record Updated
2023-10-09