The role of Ubiquitin-fold modifier 1 in plasma cell development and humoral immunity 3248

Abstract Description Following encounter with pathogen, cognate B cells differentiate into plasma cells, which home to bone marrow and secrete copious amount of high affinity antibodies leading to neutralization of pathogens. The durability of protection offered by vaccines against pathogens is positively corelated with the number and longevity of plasma cells. An expanded endoplasmic reticulum (ER) is a hallmark of plasma cells that facilitate translation, folding and secretion of high amounts of antibodies. The ufmylation pathway conjugates Ufm1 polypeptide to a target protein and modifies its function. We have previously reported that Ufbp1, a target of ufmylation, promotes plasma cell development and ER expansion. It is unclear whether the effects of Ufbp1 on plasma cell development and ER expansion are mediated through the ufmylation pathway. Here, we show that Ufm1 is dispensable for B cell development. However, development of B cells into plasma cell required Ufm1. The ER of Ufm1-deficient plasma cells were frequently dilated and swollen without ribosome. As a result, Ufm1-deficient plasma cells were defective in antibody production. Consistent with these findings, mice lacking Ufm1 in B cells, possessed decreased number of plasma cells in spleen and bone marrow and mounted defective antibody responses following vaccination. Our findings demonstrate a vital role of Ufm1 in homeostasis of plasma cells and suggest that manipulation of ufmylation pathway may improve the efficacy of vaccines. Funding Sources Supported by NIH/NIAID R01AI155774 Topic Categories Hematopoiesis and Immune System Development (HEM)