What do different types of B cells like to eat?
We’re excited to tell you about our new paper, published in The Journal of Immunology (it’s currently available for free as an open access “Advanced Article” until its official publication in an upcoming issue).
B cells are a family of immune cell that direct the rest of the immune system to attack a specific target, called an “antigen”. B cells often collaborate with another type of immune cell called a T cell. As a first step in this collaboration, a B cell must first eat the antigen so that it can digest it and then show it off to the T cell, a process called “antigen presentation”. B cells were thought to be very limited in the types of antigen particles they could inject, and it was only recently that studies showed that B cells can eat large particles through a process called “phagocytosis”.
Because of other projects in the lab, we have become interested in better understanding the limits of phagocytosis and antigen presentation by B cells. I developed a bunch of bead targets that were designed to target specific receptors that other immune cells use to phagocytose large particles. As we expected, we found that most B cells, including follicular B cells (the B cells most involved in typical antibody responses), are limited in the pathways they can use to phagocytose antigen. However, specialized B cells in the peritoneal cavity called B1 cells are unique because they are able to phagocytose other targets and can even kill bacteria.
B cells like to eating stuff they recognize
Yellow follicular B cells (top) and B1 cells (bottom) stick to and internalize pink beads that are coated with antigen recognized by their specific B cell receptor. The blue stains beads that are still on the outside of the cell. Pink beads that don’t stain blue are inside the cell.
Limiting the pathways follicular B cells can use to phagocytose antigen makes sense because it is important that B cells are directing the rest of the immune system to attack a foreign antigen target. However, it is not clear how the phagocytic abilities of B1 cells is connected to their normal function in the immune response.
Follicular B cells are picky eaters
Both follicular B cells (middle) and B1 cells (bottom) express receptors use to stick to a broad range of potential targets (but less than the professional phagocytes macrophages (top)), as shown in this expression heatmap generated from publicly available single-cell transcriptomic data (credit to our expert data collaborator Richard Zhang in Dr. Shooshtari’s research group!!). And indeed, all B cell types were good at grabbing a broad range of bead targets. But for some reason follicular B cells would only internalize targets that it bound with its B cell receptor.
We then wondered why B1 cells are capable of phagocytosing other antigens. We initially believed that B1 cells may have different receptors that allow them to recognize other targets. To our surprise, we found that follicular B cells and B1 cells have similar receptors. That leaves the question “what is different about B1 cells that allow them to phagocytose other antigens?” We believe that maybe follicular B cells have some sort of mechanism that prevents them from taking up multiple antigens. However, if this is true, this mechanism is not known, which we will try to address in future studies.
