title: Natural IgM is produced by CD5- plasma cells that occupy a distinct survival niche in bone marrow.
abstract: Natural IgM is constitutively present in the serum, where it aids in the early control of viral and bacterial expansions. Natural IgM also plays a significant role in the prevention of autoimmune disease by promoting the clearance of cellular debris. Nevertheless, the origins of natural IgM have not been precisely defined. Previous studies focused on the role of CD5(+) B1 cells in the production of natural IgM, but we show in this article that a discrete population of CD5(-) IgM plasmablasts and plasma cells in the bone marrow (BM) produces the majority of serum IgM in resting mice. These Ab-secreting cells (ASC) originate from peritoneal cavity-resident cells, because transfer of peritoneal cells completely restores serum IgM and the specific compartment of BM ASC in Rag1-deficient mice. We show that BM natural IgM ASC arise from a fetal-lineage progenitor that is neither B1a nor B1b, and that this IgM ASC compartment contains a substantial fraction of long-lived plasma cells that do not occupy the IgG plasma cell survival niche in the BM; instead, they are supported by IL-5. In summary, we identified the primary source of natural IgM and showed that these ASC are maintained long-term in a unique survival niche within the BM.
authors.affiliation: Department of Immunology, Duke University, Durham, NC 27710; and.
authors.forename: Alexander E
authors.initials: AE
authors.lastname: Reynolds
authors.affiliation: Department of Immunology, Duke University, Durham, NC 27710; and.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kuraoka
authors.affiliation: Department of Immunology, Duke University, Durham, NC 27710; and Human Vaccine Institute, Duke University, Durham, NC 27710 ghkelsoe@duke.edu.
authors.forename: Garnett
authors.initials: G
authors.lastname: Kelsoe
mesh_terms: D000818:Animals; D000921:Antibody-Producing Cells / Q000166:cytology / Q000276:immunology*; D001483:Base Sequence; D001854:Bone Marrow Cells / Q000276:immunology*; D023201:CD40 Ligand / Q000276:immunology; D018956:CD5 Antigens / Q000235:genetics; D002452:Cell Count; D002454:Cell Differentiation / Q000276:immunology; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology*; D015848:Interleukin-5 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010529:Peritoneal Cavity / Q000166:cytology; D010950:Plasma Cells / Q000276:immunology*; D017422:Sequence Analysis, DNA; D060152:V(D)J Recombination / Q000235:genetics / Q000276:immunology
chemical_list: D018956:CD5 Antigens; C526836:Cd5 protein, mouse; D018398:Homeodomain Proteins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D015848:Interleukin-5; D015850:Interleukin-6; C064658:RAG-1 protein; D023201:CD40 Ligand