Pre-mitotic genome re-organisation bookends the B cell differentiation process.

Area of Science:

• Immunology
• Cell Biology
• Genetics

Background:

• Cellular differentiation involves chromosome remodeling for lineage-specific gene expression.
• The timing of chromosome conformational changes relative to the cell cycle during lymphocyte differentiation is largely unknown.

Purpose of the Study:

• To investigate chromosome conformational changes in B lymphocytes during differentiation into antibody-secreting plasma cells.
• To determine when these changes occur in relation to the cell cycle and cell division.

Main Methods:

• Analysis of chromosome conformation in B lymphocytes at different stages of differentiation and cell cycle.
• Tracking gene-regulatory reorganization in relation to cell division and differentiation signals.

Main Results:

• Gene-regulatory chromosome reorganization occurs in late G1 phase before the first cell division.
• This conformation remains stable during rapid clonal expansion.
• A second wave of conformational change is observed during terminal differentiation into plasma cells, coinciding with extended G1 phase.

Conclusions:

• Lymphocyte cell fate is established prior to the first division through early chromosome reorganization.
• Chromosome reconfiguration precedes DNA replication and mitosis, and is linked to the gene expression program controlling differentiation and immunity generation.