Modeling human B cell development with pluripotent stem cells

Area of Science:

• Stem Cell Biology
• Immunology
• Hematopoiesis

Background:

• Generating functional B cells from human pluripotent stem cells (hPSCs) is crucial for developing novel B cell-based therapies.
• Existing methods require optimization for efficient and reliable B cell development from hPSCs.

Purpose of the Study:

• To establish an efficient protocol for developing B lineage cells from hPSC-derived definitive hematopoietic progenitors.
• To characterize the developmental stages and functional capabilities of hPSC-derived B cells.
• To investigate signaling pathways regulating B lymphopoiesis and identify potential therapeutic targets.

Main Methods:

• Generation of definitive hematopoietic progenitors from various hPSC lines.
• Flow cytometry and multi-omic single-cell RNA sequencing (scRNA-seq) for detailed cellular analysis.
• Induction of B cell maturation into antibody-secreting plasma cells.

Main Results:

• The protocol efficiently generated B cells from hPSCs, recapitulating pro-B, pre-B, and naïve B cell stages.
• hPSC-derived naïve B cells matured into antibody-secreting plasma cells with class-switching capabilities.
• Interleukin-7 (IL-7) was found to inhibit immunoglobulin heavy chain (IgH) rearrangement, impairing pre-B cell maturation.

Conclusions:

• This study demonstrates the efficient generation of functional B cells from hPSCs, providing a valuable system for research.
• The findings offer a source of staged B cells for therapeutic applications and for studying early human B lymphopoiesis.
• Distinct developmental sources, including definitive and yolk sac progenitors, contribute to human B cell lineage development.