title: CD138 and CD31 Double-Positive Cells Comprise the Functional Antibody-Secreting Plasma Cell Compartment in Primate Bone Marrow.
abstract: Plasma cells (PCs) are defined as terminally differentiated B cells that secrete large amounts of immunoglobulin (Ig). PCs that reside in the bone marrow (BM) are responsible for maintaining long-term antibody (Ab) responses after infection and vaccination, while PCs present in the blood are generally short-lived. In rhesus macaques, a species frequently used for the evaluation of human vaccines, B cells resemble those found in humans. However, a detailed characterization of BM-resident rhesus PC phenotype and function is lacking. Here, we examined Ig secretion of distinct rhesus CD138+ populations by B cell ELISpot analysis to couple phenotype with function. We demonstrate that the CD20low/-CD138+CD31+ BM population was highly enriched for antibody-secreting cells with IgG being the predominant isotype (60%), followed by IgA (33%) and IgM (7%). Transmission electron microscopy analysis confirmed PC enrichment in the CD20low/-CD138+CD31+ population with cells containing nuclei with "spokes of a wheel" chromatin structure and prominent rough endoplasmic reticulum. This panel also stained human BM PCs and allowed a clear distinction between BM PCs and short-lived peripheral PCs, providing an improved strategy to isolate PCs from rhesus BM for further analysis.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet , Stockholm , Sweden.
authors.forename: Paola
authors.initials: P
authors.lastname: Martinez-Murillo
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet , Stockholm , Sweden.
authors.forename: Lotta
authors.initials: L
authors.lastname: Pramanik
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden; Immunology Division, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
authors.forename: Christopher
authors.initials: C
authors.lastname: Sundling
authors.affiliation: Division of Clinical Research Centre, Department of Laboratory Medicine, Karolinska Institutet , Huddinge , Sweden.
authors.forename: Kjell
authors.initials: K
authors.lastname: Hultenby
authors.affiliation: Department of Orthopedic Surgery, Karolinska University Hospital , Stockholm , Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Wretenberg
authors.affiliation: Comparative Medicine, Astrid Fagraeus Laboratory, Karolinska Institutet , Stockholm , Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Spångberg
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet , Stockholm , Sweden.
authors.forename: Gunilla B
authors.initials: GB
authors.lastname: Karlsson Hedestam
keywords: antibodies; bone marrow; cryopreservation; elispot; plasma cells; rhesus macaque