Immune cells known as plasma cells are the body’s antibody factories. Following infections, plasma cells make antibodies targeted against the specific pathogenic microbes or against their antigens, in the case of vaccinations. Most plasma cells die off within weeks of forming, but some survive for decades, particularly in the bone marrow, where they continue to pump out antibodies and provide protection against the same pathogen. Plasma cells were thought to be immobile, and the nature of the bone-marrow niche supporting their long-term survival was poorly defined.
In a study published online on February 9 in Cell Reports, David Fooksman, Ph.D., and colleagues used intravital imaging to show that plasma cells in the bone marrow actually travel within the bone marrow in a unique migration pattern involving intermittent periods of high motility followed by longer stretches of confined migration or arrest. The researchers also identified factors that contribute to plasma cell movement (including the plasma-cell receptor CXCR4 and the cytokine APRIL) and to cell arrest (the receptor VLA-4). The findings suggest that plasma-cell survival depends on their motility and expression of CXCR4—both of which may increase with age. These elderly “super” plasma cells may outcompete newly formed plasma cells for factors needed to survive, perhaps explaining why older adults have weaker vaccination responses.
Dr. Fooksman is an associate professor of pathology and of microbiology & immunology at Einstein.
Posted on: Friday, March 12, 2021