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Isolation of Precursor B-cell Subsets from Umbilical Cord Blood
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Human B-1 and B-2 B Cells Develop from Lin-CD34+CD38lo Stem Cells.

Tâm D Quách1, Thomas J Hopkins1, Nichol E Holodick1

  • 1Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research, Manhasset, NY 11030.

Journal of Immunology (Baltimore, Md. : 1950)
|November 6, 2016
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Human B-1 and B-2 cells originate from a specific stem cell population. This discovery clarifies the developmental origins of B-1 cells, crucial for innate and adaptive immunity.

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Area of Science:

  • Immunology
  • Developmental Biology
  • Hematopoiesis

Background:

  • B-1 cells are vital for innate and adaptive immunity, producing natural antibodies.
  • Understanding human B-1 and B-2 cell developmental origins is challenging due to phenotypic similarities.
  • Murine studies indicate distinct progenitors for B-1 and B-2 cells.

Purpose of the Study:

  • To identify and characterize the progenitor cells responsible for human B-1 and B-2 cell development.
  • To investigate the in vivo differentiation potential of distinct human hematopoietic stem cell populations.

Main Methods:

  • Separation of cord blood and bone marrow Lin-CD34+ hematopoietic stem cells into Lin-CD34+CD38lo and Lin-CD34+CD38hi subsets.
  • Transplantation of these subsets into immunodeficient neonatal NOD.Cg-PrkdcscidIl2rg tm1wjl /SxJ mice (humanized model).
  • Phenotypic and genotypic analysis of emergent B cell populations (CD19+) in humanized mice.

Main Results:

  • Transplantation of Lin-CD34+CD38lo cells, but not Lin-CD34+CD38hi cells, generated CD19+ B cells.
  • Emergent B cells in humanized mice included distinct B-1 and B-2 cell populations found in spleen, bone marrow, and peritoneal cavity.
  • Engrafted B-1 cells displayed mature phenotypes and expressed VH-DH-JH gene compositions similar to cord blood B-1 cells, including VH4-34 usage.

Conclusions:

  • Human B-1 and B-2 cells develop from a common Lin-CD34+CD38lo stem cell progenitor population.
  • Humanized mice successfully model human B-1 cell development and Ig gene usage.
  • B-1 cells are detectable in circulation post-hematopoietic stem cell transplantation in patients with hematologic malignancies.