It Takes Three Receptors to Raise a B Cell

Trends Immunol. 2020 Jul;41(7):629-642. doi: 10.1016/ Epub 2020 May 22.


As the unique source of diverse immunoglobulin repertoires, B lymphocytes are an indispensable part of humoral immunity. B cell progenitors progress through sequential and mutually exclusive states of proliferation and recombination, coordinated by cytokines and chemokines. Mutations affecting the crucial pre-B cell checkpoint result in immunodeficiency, autoimmunity, and leukemia. This checkpoint was previously modeled by the signaling of two opposing receptors, IL-7R and the pre-BCR. We provide an update to this model in which three receptors, IL-7R, pre-BCR, and CXCR4, work in concert to coordinate both the proper positioning of B cell progenitors in the bone marrow (BM) microenvironment and their progression through the pre-B checkpoint. Furthermore, signaling initiated by all three receptors directly instructs cell fate and developmental progression.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • B-Lymphocytes* / cytology
  • B-Lymphocytes* / immunology
  • Cell Cycle Checkpoints / genetics
  • Cell Differentiation* / genetics
  • Humans
  • Precursor Cells, B-Lymphoid*
  • Signal Transduction