Identifying the precursor of natural IgM-producing plasma cells (LYM2P.736)

Abstract

Abstract Natural antibody is constitutively present in the serum, and plays an important role in the clearance of cellular debris, the early control of viral and bacterial expansions, and the initiation of T-dependent humoral responses. However, despite widespread recognition of the critical role of natural IgM in the prevention of both infectious and autoimmune diseases, the source of natural antibody long remained obscure. We have found that most serum IgM in resting mice is produced by a discrete population of IgM plasma cells in the bone marrow, a substantial fraction of which are long-lived cells that occupy a survival niche distinct from that required by IgG plasma cells. Natural IgM plasma cells originate from precursors in the peritoneal cavity, as transfer of unfractionated peritoneal washout cells completely restores serum IgM and the specific compartment of bone marrow plasma cells in Rag1-deficient mice. Surprisingly, however, transfer of purified peritoneal B1a, B1b, or B2 cells did not efficiently reconstitute serum IgM, while a distinct peritoneal B-cell population reconstituted both natural IgM and peritoneal B1a cells in Rag1-deficient mice. We propose that natural IgM plasma cells represent an “innate B-cell” population descended from yolk sac progenitors, and that natural IgM plasma cells are not the progeny of B1a cells per se but instead share an earlier common ancestor also present in the peritoneal cavity.