Most B cells are not thymus independent. That means they need help from T cells, and that's why one group of these cells is named T helpers. T helper cells promote the development of B cells stimulating them to divide, possibly to improve their antibody binding through affinity maturation, and sometimes improve their antibody function by class switching to a more effective type of antibody. As an infection clears, they will also promote the differentiation of memory cells, so you are ready the next time that bad guy shows up. In most cases when B cells bind antigen, they're going to need an extra second signal from a TH cell. That TH cell is going to provide the signal to this receptor here which is the CD40 receptor. So here we have the immunoglobulin receptor binding to an antigen, and down here we see that this is going to be internalized in a vesicle, and will be put into the interior of the cell. It will bud off. There it will be digested, and a vesicle containing an MHC II molecule will fuse with it, pick up some of that antigen, and then travel to the surface of the cell where it will fuse with the plasma membrane, and present that antigen to a TH cell. So here's the TH cell coming in, and you can see that the receptor has bound to the antigen being presented on the MHC II. We then have the binding of the CD4 onto this complex, and that stabilizes it. That's going to set off a signal to the interior, which will cause the TH cell to produce the signal for the CD40 receptor. This is sometimes called CD40 ligand, and it's sometimes called CD154. But whatever it is, it's going to bind to the receptor, and that's going to set off the second signal to the interior. It's the same kind of second signal we saw before. We're going to phosphorylate the items. We're going to recruit a variety of molecules to communicate this signal to several different cascade responses that will result in the upregulation of the B cell. Now, one thing I didn't show you here is that this is actually a conversation between the B cell and the TH cell, and it's going to set off signals to the TH cell as well. That's going to involve producing a B7 signal response to this TH cell, and that's something we're going to cover in the next part of the course when we look at T cell upregulation. So here is basically the way that a TH cell stimulates the B cell in order to upregulate it. The take-home message from this clip is that most B cells need TH instruction to produce antibodies. B cells always need signals from T cells to undergo affinity maturation, to class switch, and deform memory cells. Now, I hope you complete lecture six, do well on the final, continue on with the next course because in the next course, we will focus on how the T cells themselves activate, and we'll cover more on the specifics of T cells signaling, and how they orchestrate this whole process. Now, all of this, of course, is designed to make sure that we fight off our pathogens. Off until now, we basically described events as they happened to newly released cells, and that's the primary response shown here. The beauty of the adaptive system, however, is that the second time you encounter a pathogen, your response is much faster and much stronger, and that's what's shown here. So first, let's look at the primary response, and you can see that it begins with innate recognition and upregulation, and that's in yellow. This will then trigger the upregulation of the adaptive system but this is going to take a while, because we've got those naive lymphocytes and so there's a four to seven day lag time before they even begin proper antibody production. But hopefully, that will be a good response, and it will fight off the infection. When the infection begins to decline, so does the activity of the B cells that are producing these antibodies. During this time, the T cells will also signal the B cells to turn into memory cells, and they will also have signaled some of these cells to improve their antigen binding through affinity maturation, and approve their effectiveness through class switching. So we're going to get a variety of memory cells that had been improved in a variety of ways, and they're going to sit and wait for the next bad thing to happen. If you are reinfected with the same pathogen, you mount a secondary response. Notice it's much faster. There's only a one to three-day lag time. Also notice these memory cells are more easily activated and they've been through, as I said, affinity maturation and class switching. So instead of just having M class antibodies and here we're probably going to have a variety of G class antibodies perhaps others, and they're going to be even more effective than the first antibodies produced before because they will have improved their recognition via affinity maturation. This is an example, we are seeing here, of a first response or primary response, and the secondary response shown here in this much larger peak to the antibody production. Notice, however, that the innate response is pretty much the same both times.
