Human marginal zone B cell development from early T2 progenitors

J Exp Med. 2021 Apr 5;218(4):e20202001. doi: 10.1084/jem.20202001.


B cells emerge from the bone marrow as transitional (TS) B cells that differentiate through T1, T2, and T3 stages to become naive B cells. We have identified a bifurcation of human B cell maturation from the T1 stage forming IgMhi and IgMlo developmental trajectories. IgMhi T2 cells have higher expression of α4β7 integrin and lower expression of IL-4 receptor (IL4R) compared with the IgMlo branch and are selectively recruited into gut-associated lymphoid tissue. IgMhi T2 cells also share transcriptomic features with marginal zone B cells (MZBs). Lineage progression from T1 cells to MZBs via an IgMhi trajectory is identified by pseudotime analysis of scRNA-sequencing data. Reduced frequency of IgMhi gut-homing T2 cells is observed in severe SLE and is associated with reduction of MZBs and their putative IgMhi precursors. The collapse of the gut-associated MZB maturational axis in severe SLE affirms its existence in health.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Blood Donors
  • Case-Control Studies
  • Cell Differentiation / immunology*
  • Cell Lineage / genetics
  • Cell Lineage / immunology
  • Cells, Cultured
  • Female
  • Gastrointestinal Tract / immunology*
  • Humans
  • Immunoglobulin M / metabolism*
  • Integrin beta Chains / metabolism
  • Interleukin-4 Receptor alpha Subunit / metabolism
  • Lupus Nephritis / blood
  • Lupus Nephritis / immunology*
  • Lupus Nephritis / pathology
  • Lymphoid Tissue / immunology*
  • Male
  • Middle Aged
  • Phenotype
  • Precursor Cells, B-Lymphoid / immunology*
  • Sequence Analysis, RNA / methods
  • Single-Cell Analysis / methods
  • Transcriptome
  • Young Adult


  • IL4R protein, human
  • Immunoglobulin M
  • Integrin beta Chains
  • Interleukin-4 Receptor alpha Subunit