The journey of a marathon sleeper

A marathon sleeper who got away left some clues for Emory and University of Florida scientists to Read more

A push for reproducibility in biomedical research

At Emory, several scientists are making greater efforts to push forward to improve scientific research and combat what is being called “the reproducibility crisis.” Guest post from Erica Read more

Exosomes as potential biomarkers of radiation exposure

Exosomes = potential biomarkers of radiation in the Read more

plasma cells

Lampreys and the reverse spy problem

Call it the reverse spy problem. If you were a spy who wanted to gain access to a top secret weapons factory, your task would be to fit in. The details of your employee badge, for example, should look just right.

As described in this 2016 JCI Insight paper, Emory and University of Toronto investigators wanted to do the opposite. They were aiming to develop antibody tools for studying and manipulating plasma cells, which are the immune system’s weapons factories, where antibody production takes place. The situation is flipped when we’re talking about antibodies. Here, the goal is to stand out.

Do these guys look like good spies?

Monoclonal antibodies are classic biomedical tools (and important anticancer drugs). But it’s tricky to develop antibodies against the places where antibodies themselves are made, because of the way the immune system develops. To guard against autoimmune disease, antibodies that would react against substances in the body are often edited out.

To get around this obstacle, researchers used organisms that have very different immune systems from humans: lampreys. Emory’s Max Cooper and colleagues had already shown how lampreys have molecules — variable lymphocyte receptors or VLRs — that function like antibodies, but don’t look like them, in terms of their molecular structure.

From the paper:

We reasoned that the unique protein architecture of VLR Abs and the great evolutionary distance between lampreys and humans would allow the production of novel VLRB Abs against biomedically relevant antigens against which conventional Abs are not readily produced because of structural or tolerogenic constraints.

Senior author Goetz Ehrhardt, now at University of Toronto, used to be in Cooper’s lab, and their two labs worked together on the JCI Insight paper. 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

‘Mountain of data’ on flu vaccine responses

Bali Pulendran’s lab at Emory Vaccine Center teamed up with UCSD researchers and recently published a huge analysis of immune responses after seasonal flu vaccination (Immunity is making it available free this week, no subscription needed). Hundreds of volunteers at the Vaccine Center’s Hope Clinic took part in this study.

Note — this study looked at antibody responses to flu vaccines, but didn’t assess protection: whether study participants actually became sick with flu or not.

Our write-up is here. Immunity’s preview, from the Karolinska Institute’s Petter Brodin, is here, Cell Press’s press release is here.

Three points we wanted to call attention to:

*Long-lasting antibodies A surprising finding was how the “molecular signatures” that predict the strength of the immune response a few weeks after vaccination did not predict how long anti-flu antibodies stayed around. Instead, a separate set of signatures predicted the durability of antibody levels.

These distinct signatures may be connected with how plasma cells, responsible for antibody production, need to find homes in the bone marrow. That sounds like the process highlighted by Eun-Hyung Lee and colleagues in an Immunity paper published in July. In bone marrow samples from middle-aged volunteers, her team had found antibody-secreting cells that survive from childhood infections.

*Interfering (?) activation of NK cells/monocytes in elderly While the researchers found people older than 65 tended to have weaker antibody responses to vaccination, there were common elements of molecular signatures that predicted strong antibody responses in younger and older volunteers. However, elderly volunteers tended to have stronger signatures from immune cells that are not directly involved in producing antibodies (monocytes and ‘natural killer’ cells), both at baseline and after vaccination.

From the discussion: “This indicates a potential connection between the baseline state of the immune system in the elderly and reduced responsiveness to vaccination.” Additional comments on this from Shane Crotty in Brad Fikes’ article for the Union Tribune.

*The mountain of data from this and similar studies is available for use by other researchers on the web site ImmPort.

Posted on by Quinn Eastman in Immunology Leave a comment

Decoding lupus using DNA clues

People with systemic lupus erythematosus can experience a variety of symptoms, such as fatigue, joint pain, skin rashes and kidney problems. Often the symptoms come and go in episodes called flares. In lupus, the immune system goes haywire and produces antibodies that are directed against the body itself.

A team of Emory scientists has been investigating some fundamental questions about lupus: where do the cells that produce the self-reactive antibodies come from? Are they all the same?

In the accompanying video, Kelli Williams, who helps study the disease and has lupus herself, describes what a flare feels like. In addition, Emory researchers Iñaki Sanz, MD and Chris Tipton, PhD explain their findings, which were published this summer in Nature Immunology.

Judging by the number and breadth of abstracts on lupus at the Department of Medicine Research Day (where Tipton won 1st place for basic science poster), more intriguing findings are in the pipeline. Goofy Star Wars metaphors and more explanations of the science here.

Posted on by Quinn Eastman in Immunology Leave a comment

Following lupus troublemaker cells, via DNA barcodes

People with systemic lupus erythematosus can experience a variety of symptoms, such as fatigue, joint pain, skin rashes and kidney problems. Often the symptoms come and go in episodes called flares. In lupus, the immune system goes haywire and produces antibodies that are directed against the body itself.

The immune system can produce many types of antibodies, directed against infectious viruses (good) or against human proteins as in lupus (harmful). Each antibody-secreting cell carries a DNA rearrangement that reflects the makeup of its antibody product. Scientists can use the DNA to identify and track that cell, like reading a bar code on an item in a supermarket.

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Iñaki Sanz, MD is a Georgia Research Alliance Eminent Scholar, director of the Lowance Center for Human Immunology and head of the Rheumatology division in the Department of Medicine.

Postdoc Chris Tipton, GRA Eminent Scholar Iñaki Sanz and colleagues at Emory have been using these DNA bar codes to investigate some fundamental questions about lupus: where do the autoantibody-producing cells come from? Are they all the same?

Their findings were published in Nature Immunology in May, and a News and Views commentary on the paper calls it “a quantum advance in the understanding of the origin of the autoreactive B cells.” It’s an example of how next-generation sequencing technology is deepening our understanding of autoimmune diseases.

The Emory team obtained blood samples from eight patients experiencing lupus flares and compared them to eight healthy people who had recently been vaccinated against influenza or tetanus.

When the immune system is responding to something it’s seen before, like when someone receives a booster vaccine, the bar codes of the antibody-producing cells look quite similar to each other. A set of just a few antibody-producing cells multiply and expand, making what looks like clones. In contrast, the researchers found that in lupus, many different cells are producing antibodies. Some of the expanded sets of cells are producing antibodies against infectious agents.

“We expected to see an expansion of the cells that produce autoantibodies, but instead we saw a very broad expansion of cells with all types of specificities,” Tipton says.

To use a Star Wars analogy: a booster vaccine response looks like the Clone Wars (oligoclonal — only a few kinds of monsters), but a lupus flare looks like a visit to Mos Eisley cantina (polyclonal — many monsters). Read more

Posted on by Quinn Eastman in Immunology Leave a comment

Subset of plasma cells display immune ‘historical record’

You may have read about recent research, published in Science, describing a technique for revealing which viruses have infected someone by scanning antiviral antibodies in the blood.

Emory immunologists have identified corresponding cells in which long-lived antibody production resides. A subset of plasma cells keep a catalog of how an adult’s immune system responded to infections decades ago, in childhood encounters with measles or mumps viruses.

The results, published Tuesday, July 14 in Immunity, could provide vaccine designers with a goalpost when aiming for long-lasting antibody production.

“If you’re developing a vaccine, you want to fill up this compartment with cells that respond to your target antigen,” says co-senior author F. Eun-Hyung Lee, MD, assistant professor of medicine at Emory University School of Medicine and director of Emory Healthcare’s Asthma, Allergy and Immunology program.

The findings could advance investigation of autoimmune diseases such as lupus erythematosus or rheumatoid arthritis, by better defining the cells that produce auto-reactive antibodies.

Lee says that her team’s research on plasma cells in humans provided insights unavailable from mice, since mice don’t live as long and their plasma cells also have a different pattern of protein markers. More here.

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When bone marrow goes bad

Plasma cells live in our bone marrow. Their job: to make antibodies that protect us from bacteria and viruses. But if those plasma cells grow unchecked, that unchecked growth leads to multiple myeloma.

Sagar Lonial, MD

Multiple myeloma is a type of cancer that results in lytic bone disease, or holes in the bones. What’s more, the cancerous cells crowd out normal bone marrow resulting in anemia or a low white count, leaving a person vulnerable to infections.

Sagar Lonial, MD, an oncologist at Winship Cancer Institute, Emory University, treats people with multiple myeloma. The prognosis for people with this type of cancer is poor; however, researchers are gaining on the disease. Twenty years ago, the survival rate was two to three years; now, it’s four to five.

Lonial says one of the keys to improving patients’ prognosis is increasing their enrollment in clinical trials and better access to life-extending drugs.

Read more

Posted on by Robin Tricoles in Cancer Leave a comment