Tracking plasma cell survival
Researchers led by Osaka University use a novel tracing method to track the survival of antibodyproducing plasma cells

Osaka, Japan – Just as a fire department mobilizes in response to a reported fire, specialized immune
cells in the body mobilize in response to the introduction of foreign substances known as antigens.
Plasma cells are an important type of immune cell that release antibodies (or protective proteins) that
act to neutralize antigens. Recently, researchers from Japan have shed new light on the survival ofplasma cells in the body.
In a recent study published in Journal of Experimental Medicine, researchers led by Osaka University
have employed a novel experimental system to trace the development and longevity of plasma cells
over time.
Plasma cells are generated by the spleen and lymphoid organs in response to antigen exposure.
Many plasma cells die shortly after participating in an immune response, but a small population ofplasma cells called long-lived plasma cells (LLPCs) can survive in the body for months or even years.
The researchers sought to explore the dynamics of this LLPC population to better understand how
antibody-mediated immunity is maintained in the body.
“Our goal was to track the long-term survival of plasma cells,” says lead author of the study Takuya
Koike. “To this end, we designed a mouse model in which plasma cells in the spleen and bone marrow
were labeled by a fluorescent reporter in response to a specific drug treatment.”
The researchers monitored the survival of fluorescently labeled plasma cells in the spleen, bonemarrow, and gut for over a year and found that the frequency of fluorescent plasma cells decreased
to less than 60% within 1 month, and as low as 3%–20% within 1 year. The bone marrow appeared
to contain more fluorescent plasma cells at one year than the spleen or gut, indicating that LLPCs
may preferentially reside in bone marrow niches.
“Our results indicated that the plasma cell population likely experiences frequent turnover, with new
plasma cells replenishing the cells that are lost over time, while only a small portion of cells
differentiates into LLPCs,” explains senior author Wataru Ise. Analysis of another mouse model inwhich only newly generated plasma cells were labeled allowed the researchers to identify specificmolecular markers that can distinguish LLPCs from short-lived plasma cells.

These findings provide deeper insights into the longevity of plasma cells. Better understanding of theLLPC population may aid in the development of new vaccines that efficiently induce the generation ofLLPCs, thereby strengthening the body’s antibody-mediated immune response.

Summary: Researchers led by Osaka University generated a time-stamping method to trace thedevelopment and survival of plasma cells in the bone marrow and spleen. Using a mouse model inwhich plasma cells were fluorescently labeled in an inducible manner, they found that plasma cells
were continuously replenished by new cells, a small portion of which differentiated into long-lived
plasma cells (LLPCs). These findings may aid in the development of new vaccines that efficientlyinduce LLPCs.
Tweet: Researchers develop a new method to trace the survival of plasma cells, the body’s antibody
powerhouses
Primary Keyword: Health and Medicine
Additional Keywords: Blood, Blood plasma, Plasma cells, Bone marrow, Immune cells, Immunesystem, Immune response

Fig. 1: Most of plasma cells that arrive at bone marrow are short-lived B220(hi) MHC-II(hi) cells. A small
fraction of them become immobilized to bone marrow niches and progressively differentiate into longlived B220(lo) MHC-II(lo) cells.

Fig. 2
Plasma cells right after arriving at bonemarrow are B220(hi) MHC-II(hi), whereas
those survived for long period of time in bonemarrow become B220(lo) MHC-II(lo).

Fig. 3Plasma cells right after arriving at bone marrow
are motile and migratory, whereas long-lived
plasma cells are sessile and immobilized in thebone marrow environment.

Journal: Journal of Experimental Medicine (JEM) Dec. 14, 2022 online.
Title: “Progressive differentiation towards the long-lived plasma cell compartment in the bone marrow”
Authors: Takuya Koike, Kentaro Fujii, Kohei Kometani, Noah S. Butler, Kenji Funakoshi, Shinya Yari,Junichi Kikuta, Masaru Ishii, Tomohiro Kurosaki* and Wataru Ise* (*corresponding)
DOI: 10.1084/jem.20221717

Funded by:
Nippon Foundation
Otsuka Pharmaceutical Co., Ltd.
Grant-in-Aid for JSPS Fellows
Grant-in-Aid for Young Scientists
JSPS KAKENHI
the SENSHIN Medical Research Foundation
the Uehara Memorial Foundation
the Naito Foundation
Daiichi Sankyo Foundation of Life Science.