Human B-1 and B-2 B Cells Develop from Lin-CD34+CD38lo Stem Cells.
The B-1 B cell population is an important bridge between innate and adaptive immunity primarily because B-1 cells produce natural Ab. Murine B-1 and B-2 cells arise from distinct progenitors; however, in humans, in part because it has been difficult to discriminate between them phenotypically, efforts to pinpoint the developmental origins of human B-1 and B-2 cells have lagged. To characterize progenitors of human B-1 and B-2 cells, we separated cord blood and bone marrow Lin-CD34+hematopoietic stem cells into Lin-CD34+CD38loand Lin-CD34+CD38hipopulations. We found that transplanted Lin-CD34+CD38locells, but not Lin-CD34+CD38hicells, generated a CD19+B cell population after transfer into immunodeficient NOD.Cg-PrkdcscidIl2rgtm1wjl/SxJ neonates. The emergent CD19+B cell population was found in spleen, bone marrow, and peritoneal cavity of humanized mice and included distinct populations displaying the B-1 or the B-2 cell phenotype. Engrafted splenic B-1 cells exhibited a mature phenotype, as evidenced by low-to-intermediate expression levels of CD24 and CD38. The engrafted B-1 cell population expressed a VH-DH-JH composition similar to cord blood B-1 cells, including frequent use of VH4-34 (8 versus 10%, respectively). Among patients with hematologic malignancies who underwent hematopoietic stem cell transplantation, B-1 cells were found in the circulation as early as 8 wk posttransplantation. Altogether, our data demonstrate that human B-1 and B-2 cells develop from a Lin-CD34+CD38lostem cell population, and engrafted B-1 cells in humanized mice exhibit an Ig-usage pattern comparable to B-1 cells in cord blood.
Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research, Manhasset, NY 11030.
Tâm D
TD
Quách
Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research, Manhasset, NY 11030.
Thomas J
0000-0002-0670-4872
TJ
Hopkins
Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research, Manhasset, NY 11030.
Nichol E
0000-0002-2671-6918
NE
Holodick
Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA 19107.
Raja
0000-0001-8648-658X
R
Vuyyuru
Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA 19107.
Tim
T
Manser
Monter Cancer Center, North Shore University Hospital, Northwell Health, Lake Success, NY 11042; and.
Ruthee-Lu
0000-0002-3863-5621
RL
Bayer
Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research, Manhasset, NY 11030; tom.rothstein@med.wmich.edu.|Hofstra-Northwell Health School of Medicine, Hempstead, NY 11549.
Thomas L
TL
Rothstein
D051997:ADP-ribosyl Cyclase 1 / Q000276:immunology / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D018941:Antigens, CD19 / Q000276:immunology; D018952:Antigens, CD34 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000502:physiology*; D001853:Bone Marrow / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology*; D051927:CD24 Antigen / Q000235:genetics / Q000276:immunology; D002469:Cell Separation; D005312:Fetal Blood / Q000166:cytology; D019337:Hematologic Neoplasms / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D014183:Transplantation, Heterologous
D018941:Antigens, CD19; D018952:Antigens, CD34; D051927:CD24 Antigen; D051997:ADP-ribosyl Cyclase 1