B-Cell Receptor Complex PDF

All right, so it looks like, hopefully, we are recording in the right spot today. Fingers crossed. Fingers and toes and everything cross for every single time all the time. All right, let's see. So last class, we left off with just a handful of slides left. And you guys remember the very specific de...

All right, so it looks like, hopefully, we are recording in the right spot today. Fingers crossed. Fingers and toes and everything cross for every single time all the time. All right, let's see. So last class, we left off with just a handful of slides left. And you guys remember the very specific detail. If I'm asking about the B-cell receptor, just by itself, I'm referring to just the B-cell receptor, this immunoglobulin molecule here. Versus if I'm talking about the B-cell receptor complex, that's that functional B-cell receptor whole thing right here. So I forgot to put complex here, but basically that complex, well, it's up at the top. The complex of that is what gives you that functional. Because with just the immunoglobulin molecule, you do not have that cytoplasmic tail with ITAMs. And so if you don't have Ig alpha and beta on the side, this will not allow intracellular signaling, and the cell cannot be activated. That's why for it to be functional, you need this complex with those tails, because the tails are what gets phosphorylated. And we go through that a lot. Next week, we go through actual activation of the B-cells to differentiate them into plasma cells. Also, sorry about posting this late. I didn't realize that I had not published the class day. So it was in there. It just wasn't live. So sorry about the delay. I'm working on getting Fridays up, hopefully this afternoon. So you guys can start working on that too. And then this weekend, we'll be posting everything really early, so you guys have access to pretty much nearly everything ahead of time, so you guys can start studying early, because I know it's grad school. And you guys are focused. So secreted antibodies are produced by another alternative pattern of heavy chain RNA processing. And there is a lot more molecular steps involved. I don't think that's really necessary for you all to focus on. So again, we go through the very brief spots where we'll cut them, but we're not going to go through every single molecular step, because for you all, you guys want to be doctors. It's not critical. As long as you know that we can have a membrane-bound form and a secreted form, that's the kind of takeaway here. And so the textbook is really cool with the picture. The left side is showing that transmembrane immunoglobulin M, and this right side is the same thing, but it's showing secreted IgM here. And so we've already introduced that membrane coding region before. Your textbook is expanding on it to say that before we have that membrane coding region, we have this SC region. So thankfully, these are well-named MC, membrane coding, so you can imagine it's stuck to the membrane. And SC, or secreting, or secretion, because it is coded for being secreted, so at least those are all names that you get stuck on the MC. MC versus SC, SC is secreted, MC is attached here, too. And so that SC sequence comes before that MC. So I know the picture on an earlier slide didn't show it. We're adding it in now, basically, here. And so whether that heavy chain RNA will result in a secreted or a transmembrane occurs when we're processing that RNA transcript, and basically just depends on where we end up cleaving it, which is alternative mRNA processing here. So if we're cutting it right here, so remember that polyadenylated site, that's one of the sites that we can cut. It's well-named because we have mu, because this is IgM, and then S means secreted, versus this other polyadenylated site, which is another site that we can cut, is PA for polyadenylated mu, because it's IgM, and then the little m means it's after that membrane coding sequence. And so for this transmembrane one, if we go through as a reading RNA, and we're transcribing it into RNA, and we cut here at this cut mark after that membrane coding region, that PA mu M, that still gives us this nice tail that allows us as part of that membrane coding region. That's what gets inserted into the membrane. And so because we have that molecule, and again, it's a hydrophobic membrane coding region that can sit inside of the cell membrane of our B cell, will give us that transmembrane version, versus if we cut at that earlier site where we're going through and transcribing that RNA, and we cut here, it gets rid of that membrane coding region and just gives us the secretion coding, it does not have that hydrophobic membrane coding region, we've cut it off, you don't have it there anymore. And this specific polyadenylated tail is not something that will bind onto the membrane, and so that is how we end up creating what is known as that secreted form. And so when our B cells will differentiate into plasma cells, we start to get those signals where we stop processing and stop reading the RNA transcript all the way through this PA mu M for cutting that membrane bound immunoglobulin, we start stopping all production earlier, so that all, why we have that bigger Golgi apparatus in plasma cells, we're creating more of this secreted version that we will pump out to the surface and rather than having it bind onto that cell membrane surface as our B cell receptor or immunoglobulin molecule, we are secreting it out now in its soluble form.