CD stands for "Clusters of Differentiation". Also "Certificates of Deposit" and "Compact Disc", but those subjects are outside the bounds of this blog. The CD nomenclature is principally applied to cells of the immune system and has a long back story that begins with entities called monoclonal antibodies - a topic that I could greatly expand on. However, I'll try to make it short.
When a foreign protein enters our bodies, we respond with a burst of antibody production. Many different antibodies may bind to this single molecule. That's because, as I mentioned in the last post, proteins are complicated with many nooks, crannies, cavities, and protrusions. A single antibody is capable of recognizing and binding to only one of these surface features as shown in the illustration on the right. It is for this reason that the antibody response is called "polyclonal", meaning that many different B cells, each with a distinct recognition site, bind to the antigen, each eventually elaborating different antibodies.
To make it "monoclonal", restricting the response to one B cell and its descendants, you would have to isolate a single B cell, place it in a culture vessel, and have it reproduce many times to yield a clone of identical progeny. While this approach is feasible in theory, and actually was done in practice, its utility depends on the ability for B cells to reproduce indefinitely in a culture vessel, something that it is incapable of. That's because all differentiated human cells have a limited lifespan. Most cancer cells, by contrast, are immortal, and can grow in culture forever. In 1975, Cesar Milstein, an Argentinian immigrant, and Frederick Kohler, a German postdoctoral fellow in Milstein's laboratory at the Medical Research Council in the United Kingdom, fused a mouse B cell with a cancerous plasma cell, to create a hybrid that was immortal and capable of spitting out loads of antibody. For their efforts, they shared two-thirds of a Nobel Prize in 1984.
Why was their achievement so important? Monoclonal antibodies can be produced in great quantities and have an exquisite specificity. As such, they can act as "magic bullets" and home in on a specific therapeutic target. Since 1985, more than 73 monoclonals have been approved by governmental agencies, 33 of these in the last four years alone. Rheumatoid arthritis, multiple sclerosis, psoriasis, asthma, and several kinds of cancers are some of the diseases that are being treated by these reagents. Six out of 10 of the best selling drugs in the world are monoclonals. They're also extremely useful in diagnosis, acting as probes that allowing scientists to identify specific cells. (For a more extensive discussion of monoclonal antibodies, I recommend "The Lock and Key of Medicine: Monoclonal Antibodies and the Transformation of Healthcare" by Lara V. Marks, Yale University Press, 2015).
And that's where clusters of differentiation comes in (did my digression distract you?). As monoclonal antibodies became more widely used, a number of laboratories used them to characterize the cell surface proteins of a variety of immune cell types. Many of these cell types were indistinguishable microscopically They could only be told apart by the monoclonal antibodies that bound to the antigens that they bore on their surface. With many laboratories working with many monoclonals and a host of cell types, it soon became a mess. For example, lab A identified an immune cell that reacted with a specific monoclonal antibody that they had prepared. Lab B found a similar looking cell but used a different antibody. Were the two cells the same? Were the two antibodies binding to the same antigen? No one knew. There was a further contribution to uncertainty. Each laboratory gave its own favorite name to the cells they had characterized and the antigens that they had detected. Confusion reigned.
In 1982 immunologists met together in Paris in an effort to resolve this chaos. The meeting was called the "First International Workshop and Conference on Human Leukocyte Differentiation Antigens" and the result was the CD nomenclature. The term "Workshop" is appropriate. Each monoclonal antibody was tested in the lab. When two or more were found to bind to the same molecule, a CD number was assigned to that antigen. Since 1982, nine additional workshops have been organized. The last was held in Australia in 2014. Over that time, some 370 CD numbers have been allocated.
(I admit to having been bothered by the term "clusters of differentiation", both the "clusters" and "differentiation" parts. People using the term in different ways just added to my confusion. I eventually learned that surface proteins are often referred to as differentiation antigens. The cluster part of the term comes from the fact that the same molecule, most often a protein, may be bound by a group/cluster of different monoclonals (remember that proteins present a variety of different surface features and therefore may be recognized by different antibodies). The important point to remember is that CD's refer to surface proteins that can be used to classify different cell types. An article in Wikipedia states that some prefer to call CD's "Classification Determinants", a better name in my opinion.)
You'll recall that the heavy chain gene bears multiple constant regions. When a B lymphocyte is first activated, it caries a Cm segment on its heavy chain, and produces antibody of the IgM class (some IgD may also be made, but only in small quantities). IgM antibodies look a lot different than the ones that I've described previously. They are pentamers, consisting of five Y shaped antibody molecules bound together (see the figure). Later on, as the B cell matures, it can change its heavy chain constant region. By cutting out the other C regions, it can append one of the other C regions onto the heavy chain gene. The antibodies produced as a result of this switch may be IgG, IgE or IgA depending on which C segment remains abutted to the remainder of the gene. But remember, the variable regions, the antigen binding site, remains as it was, meaning that the resultant antibody retains its specifity.
You may wonder why "class switching" occurs, especially since switched antibodies continue to bear the same variable region. The answer is that the various classes of antibodies have different functions. I'll discuss these functions as well as memory cell formation in the next positing.