Millions of B cells that have passed through multiple checkpoints in the bone marrow will now enter lymph nodes. They're explosive devices, like naval mines, each capable of destroying a specific microbe or microbial product that they've targeted by virtue of the receptors bound to their surfaces. Most, however, will never encounter their specific prey. After a few months these unfulfilled B cells die, to be replaced by new generations that are constantly being spawned in the bone marrow.
B cells that have found and bound a target molecule first need to become activated, meaning that they have to undergo some drastic changes in order to transform into death dealing devices. Activation causes a burst of proliferation and the ability of individual cells to churn out soluble antibodies in enormous numbers (according to Abbas et al, a B cell can give rise to 5,000 descendants that can collectively synthesize a trillion antibody molecules in a week). The change is so dramatic that immunologists even give fully activated cells their own distinct name - "plasma cells". It's important to understand that a plasma cell continues to bear the same rearranged gene before and after it has met its cognate antigen. As I'll elaborate, this means the antibodies it produces are essentially the same as those borne by the receptor affixed to its surface (although, intriguingly, they may be improved under some circumstances).
But even after all it's been through, binding to an antigen is a necessary but not a sufficient action for activation of B cells to occur. One of two possible additional steps is needed. One route to activation requires the participation of a T cell, the second type of adaptive immune cell that I'll discuss in many subsequent posts. The other utilizes parts of the innate immune system. This second activation pathway is called "T cell independent". I'll discuss it next.
T cell Independent Activation
The antigens that generate the T cell independent activation pathway are generally repetitive chemical units, polysaccharides or lipids, borne on the surface of bacteria. As described in the last post, binding to these molecules causes the B cell receptors to cluster, priming the cells for activation. The actual activation process can be promoted by cytokines secreted by cells like macrophages that have detected an invader. Alternatively, a B cell that has detected a microbe can be activated by the simultaneous binding of its own Toll-like receptors to the antigen. Yet another source of co-activation are components of the complement system that are bound to a microbe. These are recognized by special receptors on the B cell surface. The last two of these routes to activation are illustrated in the cartoon on the right. You'll notice that all these routes to T cell independent activation involve participation of the innate immune system, emphasizing the close relationship between the two.
From what I can gather from the sources that I have access to, B cells activated via the T cell independent pathway don't marshal as robust an immune response as is provoked by the T cell dependent route. While B cells activated via the T cell independent mechanism proliferate and secrete antibodies, they appear incapable of undergoing two processes that I'll discuss in a coming post: class switching and somatic hypermutation. They also can't become memory cells, another topic that I'll have to put off for another day . However, T cell independent activation of B cells is fast. And it is often sufficient to meet the challenge of some bacterial infections.
T cell Dependent Activation
T cell dependent activation is generally promoted by proteins. That's because proteins don't often bear repetitive antigenic groups. B lymphocytes take up some proteins from invasive microbes, process them, and present them to helper T cells. In turn, the T cells help complete B cell activation. The B cells activated in this way can undergo class switching and hypermutation, the terms I introduced above. How all this unfolds and what it means will be the subject of the next post.