T Cell Dependent B Cell Activation
I've had some difficulties with this topic. Abbas et al's book describes the subject in great detail and I've found it hard to follow. Sompayrac devotes only a paragraph to it. The clearest, and simplest, explanation comes from Erridge's book, supplemented by material from Wikipedia. Here's what I learned.
The antigens that invoke a T-dependent activation of B cells are mostly proteins. That's because proteins are not repetitive molecules in the same way that polysaccharides are. That is, their surface consists of a great variety of distinct three dimensional features. A different receptor binds to each one. Therefore, when a B cell encounters a protein antigen, it can't cluster its B cell receptors in the same way that it does when binding a polysaccharide. Instead, when a B cell receptor binds to a protein, it internalizes it, meaning that it draws it into its interior. Subsequently it processes the protein into small fragments that it displays on the cell surface (much more on this later when I talk about T cell functions). These fragments can be recognized by helper T cells. Upon recognition, the T cells become active, secrete cytokines, and, at the same time, express a ligand on their surface called CD40L. B cells have a receptor for this ligand called CD40, with the result that the T cell and B cell bind to each other. This in turn causes the B cells to become active. They begin dividing and churning out antibody. This process is complex and takes place over several days. The cells make good use of this time. They produce antibodies that are much better at binding antigen and more versatile than those produced via the T cell independent pathway, employing a mechanism that I'll describe below.
What's with the CD nomenclature? You promised to trip light on the jargon and not use abbreviations. I'm glad you asked because it offers me the opportunity to discuss two other topics of interest. However, because the explanation is lengthy, I'll put it off until the next post.
Recall that antibodies are constructed from proteins that are specified by heavy and light genes. The heavy chain genes carry nine multiple constant regions with names like Cm, Cd, Ca, etc.. Newly activated B lymphocytes synthesize heavy chains bearing a protein coded for by the Cm region. Therefore the antibodies that they produce are said to members of the IgM class, where the "Ig" part indicates "immunoglobulin" and the "M" stands for the Cm constant region. Again, I'm going to put off a discussion of how the different classes of antibodies differ from one another and what roles they play for later. For now it's important to know that the class of an antibody is dependent on the heavy chain it carries, and that while undergoing T cell dependent activation, the B cell can switch the class of its heavy chain (Heavy chain switching doesn't occur in T cell when the B cell is activated in a T cell independent manner). This switching occurs via DNA rearrangement, causing the VDJ variable region of the heavy chain to become joined to the constant region. During the switch, rearrangement the variable region remains as it was, retaining its specificity for whatever antigen promoted the activation of the B cell. Any of the nine constant regions can be appended to the variable region, resulting in the production of different class of antibody. Each of these classes play a different role as I'll explain next time.
However, class switching isn't the only change that occurs to the antibody genes in T cell dependent activated B cells. The variable region also undergoes a change in DNA. As a B cell divides, some of the variable region DNA sequence begins to change (mutate) at a rate at least 1,000 times that of normal genes. The end result may be a variable region that differs by as much as 5% from that with which it began. Since these changes are more or less random, any given cell may carry an improved antibody (one which binds more tightly to its cognate antigen) or one that isn't any better at binding than it started out with, or one that it is worse or loses its affinity for the antigen altogether. If that's the case, how does hypermutation improve the immune response?
The answer is: via selection. Those B cells that have managed to acquire an improved antibody via hypermutation continue to interact with T cells, and they signal via CD40L to remain alive. In the absence of a good T cell interaction, the B cells will cease proliferating and die. In this way, B cells with "improved" antibodies will dominate the population.
Next time, I'll discuss the benefits of class switching, what "CD:" means, and immunological memory.