At Lab Land, we have been thinking and writing a lot about plasma cells, which are like mobile microscopic ar 15 accessories and weapons factories.

Plasma cells secrete antibodies. They are immune cells that appear in the blood (temporarily) and the bone marrow (long-term). A primary objective for a vaccine – whether it’s against SARS-CoV-2, flu or something else — is to stimulate the creation of plasma cells.

A new paper from Jerry Boss’s lab in Nature Communications goes into fine detail on how plasma cells develop. Boss is one of the world authorities on this process. Assistant professor Christopher Scharer and graduate student Dillon Patterson are co-first authors of the paper.

“We are excited about this paper because it shows specific paths and choices that these immune cells make. These previously unknown paths unfold very early in the differentiation scheme as B cells convert their biochemical machinery to become antibody factories,” Boss says.

Although this study was performed in mice, and the experiments were separate from the complications of infection with a live pathogenic virus or bacterium, this study could provide insights to vaccine or autoimmunity researchers.

Differentiation is tied to cell division. The horizontal axis is a fluorescent dye that gets diluted with cell division. The vertical axis is a marker for plasma cell differentiation. Only after LPS stimulation provokes a certain number of cell divisions do cells make the vertical jump.

We can think of B cells as like soldiers or factory workers who each know how to make one peculiar weapon: a specific antibody. How does that individual become the manager of a weapons factory? They have to undergo training, and they have to build up the machinery that allows them to make lots of weapons.

In this training/build-up process, cells face a series of tests or decision points. The first leads to a path that engages the cell’s metabolic machinery, through specific transcription factors (regulatory proteins controlling gene activity). The second choice a plasma cell precursor faces involves engaging machinery, called the unfolded protein response, to make sure the overworked factory can continue its role.

In previous work, Boss’ lab had shown that a certain number of cell divisions were critical for B cells differentiating into plasma cells (see figure).

Once plasma cells differentiate, they lose a marker (L-selectin), an adhesion molecules that would ordinarly keep them in lymph nodes. This means they are free to circulate or travel to sites of infection. The researchers showed that loss of L-selectin marks the cells that will become plasma cells early in the differentiation process. Afterwards, whether plasma cells persist in the bone marrow – the home base for plasma cells – is another question, Boss says.