Antibody production: an endurance sport

To understand recent research from immunologist Jerry Boss’s lab on antibody production, think about the distinction between sprinting and long-distance Read more

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Jeremy Boss

Antibody production: an endurance sport

Antibodies defend us against infections, so they often get described as weapons. And the cells that produce them could be weapon factories?. To understand recent research from immunologist Jerry Boss’s lab, a more appropriate metaphor is the distinction between sprinting and long-distance running.

Graduate student Madeline Price in Boss’s lab has been investigating how antibody-producing cells use glucose – the simple sugar– and how the cells’ patterns of gene activity reflect that usage. Cells can use glycolysis, which is inefficient but fast, analogous to sprinting, or oxidative phosphorylation, generating much more energy overall, more like long distance running.

As Boss and Price point out:

Immunology + Molecular Pathogenesis graduate student Madeline Price

Glycolytic metabolism produces 2 molecules of ATP per molecule of glucose, while oxidative phosphorylation produces 36 molecules of ATP from the same starting glucose molecule. Where oxidative phosphorylation generates more energy from ATP, glycolysis generates metabolic intermediates that are also useful for rapid cellular proliferation.

In their recent paper in Cell Reports, they lay out what happens to B cells, which can go on to become antibody secreting cells (ASCs), after an initial encounter with bacteria. The B cells first proliferate and upregulate both glycolysis and oxidative phosphorylation. However, upon differentiating, the cells shift their preference to oxidative phosphorylation. Read more

Posted on by Quinn Eastman in Immunology Leave a comment

Plasma cells, antibody factories

Immune cells that serve as antibody production factories, also known as plasma cells, are the focus of a recent Nature Immunology paper from Jeremy Boss and colleagues.

Plasma cells also appear in Ali Ellebedy and Rafi Ahmed’s recent paper on the precursors of memory B cells and Eun Lee’s work on long-lived antibody-producing cells. In addition, plasma cells appear prominently in Larry Boise’s studies of myeloma, because myeloma cancer cells are thought to come from plasma cells and have a similar biology.B cell methylation

The Boss lab’s paper focuses on patterns of methylation, modifications of DNA that usually help turn genes off. In comparison with resting B cells, plasma cells need to turn on lots of genes, so their DNA methylation level goes down when differentiation occurs (see graph). PC = plasma cells, PB = plasmablasts. DNAme indicates the extent of DNA methylation. Read more

Posted on by Quinn Eastman in Immunology Leave a comment

Risk triangle: immune gene, insecticide, Parkinson’s

Genetic variation and exposure to pesticides both appear to affect risk for Parkinson’s disease. A new study has found a connection between these two risk factors, in a way that highlights a role for immune responses in progression of the disease.

The results are published in the inaugural issue of NPJ Parkinson’s Disease.

The findings implicate a type of pesticide called pyrethroids, which are found in the majority of commercial household insecticides, and are being used more in agriculture as other insecticides are being phased out. Although pyrethroids are neurotoxic for insects, exposure to them is generally considered safe for humans by federal authorities.

The study is the first making the connection between pyrethroid exposure and genetic risk for Parkinson’s, and thus needs follow-up investigation, says co-senior author Malu Tansey, PhD, associate professor of physiology at Emory University School of Medicine.

The genetic variation the team probed, which has been previously tied to Parkinson’s in larger genome-wide association studies, was in a non-coding region of a MHC II (major histocompatibility complex class II) gene, part of a group of genes that regulate the immune system.

“We did not expect to find a specific association with pyrethroids,” Tansey says. “It was known that acute exposure to pyrethroids could lead to immune dysfunction, and that the molecules they act on can be found in immune cells; now we need to know more about how longer-term exposure affects the immune system in a way that increases risk for Parkinson’s.”

“There is already ample evidence that brain inflammation or an overactive immune system can drive the progression of Parkinson’s. What we think may be happening here is that environmental exposures may be altering some people’s immune responses, in a way that promotes chronic inflammation in the brain.”

For this study, Emory investigators led by Tansey and Jeremy Boss, PhD, chair of microbiology and immunology, teamed up with Stewart Factor, DO, head of Emory’s Comprehensive Parkinson’s Disease Center, and public health researchers from UCLA led by Beate Ritz, MD, PhD. The first author of the paper is MD/PhD student George T. Kannarkat.

The UCLA researchers used a California state geographical database covering 30 years of pesticide use in agriculture. They defined exposure based on proximity (someone’s work and home addresses), but did not measure levels of pesticides in the body. Pyrethroids are thought to decay relatively quickly, especially in sunlight, with half-lives in soil of days to weeks. Read more

Posted on by Quinn Eastman in Immunology, Neuro Leave a comment