CD226+ B-cells or not CD226+ B-cells, that is the question
So what exactly am I doing here? Oh that’s right, research. In the spirit of expanding the vast body of scientific knowledge, I will now tell you my exact research question, and then spend the next five weeks performing experiments to determine that question’s answer. After enjoying a few weeks in the lab learning, I’m now embarking on the wonderful journey towards the research conclusion.
You’ll have to learn a little bit more about epstein-barr virus before I explain the research question…
Epstein-barr virus, or EBV, infects over 95% of human adults. Most people acquire EBV around age three, when it causes a mild immune response. However, in today’s germophobic society, some people do not contract EBV until their teenage years, when it provokes a much stronger immune response. This EBV-induced teenage sickness is known as infectious mononucleosis, more commonly called mono.
The first time a person contracts EBV, whether as a three year older or a teenager, is termed the primary infection. During primary infection, EBV infects both epithelial cells and B-cells (B-cells, or B-lymphocytes, are an integral part of the human immune system). Even after the primary infection, EBV remains within some B-cells for the rest of the person’s life. This isn’t to say that we remain sick all the time; that would be a most unfortunate situation. The virus, instead of actively infecting new epithelial cells and B-cells and making you feel sick, remains “hidden” within certain memory B-cells. As the virus is not actively propagating, infecting new cells, and causing sickness, the virus is said to be in the latent stage. Latency is completely different from the lytic stage, when the virus is actively reproducing and infecting epithelial cells, such as during mono.
Occasionally, the virus tries to use the long-lived (or immortalized) memory B-cell that it hides in to re-establish an active infection, causing the infected B-cell to replicate and proliferate. Hmmmm, long-lived, proliferating B-cells? Doesn’t that sound like cancer? In fact, that’s exactly what it is. Fortunately, most people’s immune systems do a pretty good job of beating back these sporadic EBV uprisings, and EBV remains blissfully latent for the rest of their lives.
But what about those people who have compromised immune systems, who are immunosuppressed? The EBV-infected, immortalized B-cells can then proliferate freely, causing a whole host of B-cell lymphomas. Such cancers mostly occur in persons who are on immunosuppressant drugs for organ transplants, have AIDS or malaria, or are malnourished. Since EBV causes lymphomas during immunosuppression, EBV is called a co-factor for these cancers. Burkitt’s Lymphoma, the most common childhood malignancy in sub-Saharan Africa, has an EBV co-factor. Nasopharyngeal carcinoma, another cancer with an EBV co-factor, is frequent cancer in China and Eastern Asia. Here in America, Hodgkin’s Lymphoma is the most well-known cancer associated with EBV.
For my work, I am looking at whether certain subpopulations, or types, of B-cells are more sensitive to infection and immortalization with EBV than others. I am particularly interested in a B-cell marker known as CD226. In an experiment, our lab noted that only about 3% of normal, uninfected B-cells have CD226. However, almost 100% of EBV-infected, immortalized B-cells in vitro (known as lymphoblastoid cell lines or LCLs) are CD226 positive. In a preliminary experiment run over the last couple of weeks, I’ve found that CD226 becomes increasingly expressed over time in populations recently infected with EBV.
So the now the research question is, “is CD226 upregulated by EBV, or are cells that are CD226+ in the first place more sensitive to EBV, and grow out into LCLs?” In this case, upregulated simply means that EBV causes B-cells to express more CD226 by causing the CD226 gene to be expressed more. I’ve come up with 2 hypotheses that represent what could happen in each case…
Hypothesis 1: EBV Upregulates CD226 Expression
If B-lymphocytes are sorted into CD226+ and CD226- populations and then infected, both populations will increasingly express CD226 during outgrowth into LCLs, especially the CD226- population
Hypothesis 2: B-cells that display CD226 develop into LCLs when exposed to EBV
If B-lymphocytes are sorted into CD226+ and CD226- populations and then infected, the 226+ population will develop into CD226 expressing LCLs, while the 226- population will die off and not experience outgrowth into LCLs.
Of course, the increased CD226 expression in LCL could also be a combination of both upregulation and preferential development of CD226+ cells into LCLs! That’s where this gets complicated. Stay tuned over the next few weeks (and perhaps into the fall) to find out the results.
Some notes of correctness: The term “immortalized” to refer to latently-infected B-cells is somewhat disputed, as these cells do have extremely extended life spans but do not actually proliferate indefinitely. Also, I hope you will excuse my occasional personification of the virus, which I assure you I only employed in the interest of simplicity :)
