History of the B-cell in its 50th anniversary year
Prof Max Cooper - Emory University, Atlanta, USA
My talk related to the fact that it’s been fifty years since we recognised B-cells as a separate lymphocyte lineage that collaborates with T-cells. I talked about how we had gone back and looked to see if we could find the roots of our immune system and which came first in evolution, B-cells or T-cells. So we did studies in lampreys and hagfish, with whom we last had a common ancestor about 500 million years ago, and we found that they have T-cells and B-cells, they have the genes and the developmental patterns that our T and B-cells have except they use different kinds of receptors. They have receptors, each lymphocyte expresses a unique one for an antigen, that are made by leucine-rich repeat and not by immunoglobulin domains as our antibodies and T-cell receptors and B-cell receptors are made. So it told us that T and B-cells have been inseparable companions for more than 500 million years, even though we’ve only known about them for the last fifty years. So it was a tangential sort of talk relative to the other talks this morning that were more directly related to B-CLL.
Can you tell me more about your research over the years and what some of the key findings have been?
My colleagues and I were the first to really split clearly T and B-cell lineages and that changed our whole view of how the immune system developed. It changed our view of how malignancies occur, how defects in T-cells or B-cells or both might help explain immuno-deficiency diseases. It raised questions that we’ve been trying to answer since: what do T-cells use to see antigens if they didn’t make antibodies? That took about twenty years to discover. Where do B-cells originate in mammals? That took about ten more years to find the bursa equivalent because the split is not in chickens, they have a thymus and a bursa of Fabricius and that allowed a clean dissection of thymus-derived T-cells, bursa-derived B-cells.
In the time since my colleagues and I worked on class switching; we identified that the hematopoietic tissues were the sites where B lineage cells originate and that let us help define early stages of B-cell development. So that’s the sort of thing that I’ve been working on since, as have many immunologists.
And for CLL patients, what do you think the exciting things in the pipeline are right now?
The biggest excitement of this meeting are the new agents, to block signalling pathways in particular by B-cell receptors. That took a long time to be defined and now those are now paying off in a big fashion.
Is there a take home message?
The take home message is that T and B-cells have been constant companions for over 500 million years ago and that didn’t come about and maintain itself by accident. So they have to be viewed, even in malignancies like B-cell leukaemia, they have to be viewed in the context of the co-operative interaction of T-cells and B-cells.
What are your plans for research into the future?
Well one of the things that we’re interested in is using these lamprey antibodies for biomedical purposes. The antibodies that they make are totally different from ours, are easy to manipulate, tough as nails and they are highly specific. Because we last had a common ancestor with lampreys more than 500 million years ago their antibodies are not tolerized to… their B-cells are not tolerized to self-antigens that we have. So they can make antibodies to antigens that are cryptic or not accessible to our antibodies. So we think because of their specificity, unusually that’s different from our antibodies, we would be able to use them for therapeutic purposes. For example, we’re hoping to make lamprey antibodies that see cancer antigens that can be used to target cancer cells in a unique way. So that’s one of the things that we’re interested in: trying to turn this curiosity-driven research trip into something of therapeutic value.
