New publication from us

note: this post is part of our ongoing experiment with SciCom and social media.

We’re excited to tell you about our new study, published today in Cell Reports.

We, like other Immunology labs, spend much of our time trying to understand how the immune system decides what it’s going to attack and how. T cells and B cells are two families of immune cells that are both responsible for identifying a specific target (called an “antigen”) and directing the immune system to attack it, although they go about that role in very different ways. Still, under most circumstances, B cells and T cells that recognize the same antigen collaborate with each other to determine how the immune response will develop, and this impacts the effectiveness of the resulting response. Figuring out how this is achieved is a very active field in immunology.

 
Lead author and recent PhD grad. Dr. Rajiv Jain.

Lead author and recent PhD grad. Dr. Rajiv Jain.

 

Our study, led by recent PhD grad Dr. Rajiv Jain, started with a very simple question:

Does the immune response to a self-antigen, in this case to myelin oligodendrocyte glycoprotein (MOG), a protein found in the central nervous system (CNS – brain and spinal cord), develop differently compared to a response to a more “normal” foreign antigen?

We had several reasons for wanting to know the answer to this question. One is that we and others use MOG protein to induce CNS autoimmunity in animals to model human diseases such as Multiple Sclerosis (MS) (see more about that here, and about our MOGtag proteins here). We have been using these models to try to understand how B cells contribute to disease, and so far have focused mostly on the B cells that infiltrate the inflamed CNS (see here and here). However, after a few surprises (to us, at least) it became apparent that we needed a more in-depth understanding of the basics of the B cell response to MOG antigen.

A second motivation for this study is that, in addition to our more MS and related disease-oriented studies, we are also very interested in simply understanding how the immune system works and how it tailors its response to a specific target. So far, nearly all investigations of this process (including our own primary and collaborative studies – see here, here, and here) have studied the response to a very short list of model target antigens. We had a hunch that the response to MOG might be different enough to be a useful tool to dissect the signals responsible for determining immune outcome, allowing us to address these types of questions from a different perspective than we or others have used previously.

Jain Graphical Abstract.jpg

It turned out that our hunch was correct. When Rajiv immunized mice with MOG protein, the B cell response was initiated relatively normally compared to the standard model foreign antigen, but it wasn’t sustained. Instead, the organized B cell response collapsed early into what at first looked like Memory B cells, specialized cells that respond the next time you see the same antigen. However, it turned out that these cells didn’t live very long, so the memory response to MOG failed. We performed some experiments to determine which features of the B cell response to MOG were controlled by the T cell partner, and also manipulated the antigens in different ways to alter the outcome of the response.

So, why is any of this important? To other Immunologists, this study represents another step forward in our cumulative understanding of how the immune system controls the outcome of its response to a target antigen. This is inherently important to those of us who want to understand how biology works. It’s harder to explain the value of fundamental research like this to those outside of the science community. If this were a standard press release, this is the part where we’d say something like “in 20 years, these findings could result in better treatments for autoimmune disease, or better vaccines”. This could, in fact, turn out to be the case; fundamental studies like ours asking similar questions about how immune cells signal to each other led to the development of Checkpoint Inhibitors – and this work was just awarded the 2018 Nobel Prize in Physiology or Medicine for the way they have revolutionized the treatment of many cancers. In fact, if you dig into the history of nearly every major advance in medicine or technology you will find similar foundations on so-called curiosity-based research.

Science is a group effort! Rajiv (top row, second from the left) led the project, and Yodit (top row, second from left), Heather (Bottom row, left), and Kate (second from left) all contributed to this publication. Past undergrad Emiliano Romanchick (not in this picture) also contributed to the study and is an author on the paper.  Want to be a part of the team? We’ll be looking for a new PhD and undergraduate trainees soon!

Science is a group effort! Rajiv (top row, second from the left) led the project, and Yodit (top row, second from left), Heather (Bottom row, left), and Kate (second from left) all contributed to this publication. Past undergrad Emiliano Romanchick (not in this picture) also contributed to the study and is an author on the paper.

Want to be a part of the team? We’ll be looking for a new PhD and undergraduate trainees soon!

Nevertheless, there are more short-term outcomes from our new study for our own work. First, we’re applying what we’ve learned about the anti-MOG B cell response to our investigations of B cells in autoimmune disease. The findings from this study will help PhD student Yodit Tesfagiorgis to refine the questions she’s asking in our more disease-oriented work. Also, we now have a unique model to study the signals T cells use to affect what B cells do in an immune response. Post-doc Dr. Kate Parham is pushing these investigations forward and she already has some tantalizing results that we’re looking forward to sharing with you one day in a future publication.

 A Note About Funding:

The work we do is entirely dependent on your support, whether it be through your taxes or donations to funding agencies. Thank you! Lead author Rajiv Jain was funded by a studentship from the MS Society of Canada. They also fund co-authors Yodit Tesfagiorgis (PhD Studentship) and Kate Parham (Post Doctoral Fellowship).

Operating funding for the lab (covering the actually cost of experiments, not just people) has come from a grant from the Canadian Institutes of Health Research.