Regulation of Anti-viral Immunity – A study of B Cells

“The importance of antibodies has been the centre of attention recently during the SARS-CoV2 pandemic and major efforts have been made to understand effective antibody responses,” Dirk Brenner

In a study to understand more closely the inner workings of the antibody immune response, a research team led by Professor Dirk Brenner, Deputy Head of the Department of Infection and Immunity (DII) at the Luxembourg Institute of Health (LIH) and Professor of Immunology and Genetics at the University of Luxembourg, set out to find key differences in the metabolism of two closely related immune cell subsets, the B cells FoB and MZB.

‘Follicular’ B cells (FoB) tend to reside in small aggregations alongside other immune cells in places like the spleen and lymphnodes, while ‘marginal zone’ B cells (MZB) make up only about 5-10% of the B cells in a spleen, where they can rapidly respond to blood-borne viral particles and invading bacteria.

Discovering unique cell characteristics

The authors focused on metabolic differences between both B cell subsets up to the point of synthesis of new molecules and the breakdown and removal of others, by targeting the production of a key chemical, glutathione; this normally helps to maintain the delicate balance of reactions that regulate cell metabolism. By tipping the balance, researchers were able to look for differences that were unique to each cell type.

When glutathione production was inhibited in the MZB cells of mice, a more significant impact was seen on normal cell development and maintenance, leading to an overall cell loss. FoB cells behaved in a more adaptive fashion, reprogramming their normal metabolic pathway so that they actually began to behave more like regular MZB cells. The downside for FoB cells however, was that this also led to an accumulation of defective mitochondria (the powerhouse of the cell), ultimately rendering them ineffective when exposed to viruses.

“Our work highlights B cell-specific alterations that offer novel insights for the understanding of the role of glutathione in the regulation of B cells function and defects upon viral infections,” summarised Dr Davide Franchina, first author of the study from Professor Brenner’s team at the DII.

By continuing to build knowledge of these crucial gatekeepers, researchers can begin to translate the findings into novel treatment strategies for viral diseases such as SARS-CoV2, with tangible patient outcomes in the future.

This study was supported by the FNR’s INTER-CORE [(C18/BM/12691266) program]. The work was also partially supported through intramural funding of LIH through the Ministry of Higher Education and Research (MESR) of Luxembourg.

“Glutathione-dependent redox balance characterises the distinct metabolic properties of follicular and marginal zone B cells”. Published in Nature Communications, April 4.

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