Clonal selection in the germinal centre by regulated proliferation and hypermutation

Area of Science:

• Immunology
• Molecular Biology
• Cell Biology

Background:

• B lymphocytes undergo clonal expansion and immunoglobulin gene diversification in germinal centers (GCs) during immune responses.
• High-affinity B cells are selected through iterative cycles of division, hypermutation, and selection in the GC dark and light zones.

Purpose of the Study:

• To investigate the regulation of clonal expansion and hypermutation during interzonal germinal center cycles.
• To determine if cell division and hypermutation extent are proportional to antigen capture and presentation.

Main Methods:

• Utilized a transgenic strategy to quantify cell division within germinal centers.
• Employed a photoactivatable fluorescent reporter to examine hypermutation rates.
• Combined these methods to study B cell dynamics in germinal centers.

Main Results:

• Found that both cell division and hypermutation are directly proportional to the amount of antigen captured and presented by GC B cells.
• Demonstrated that antigen presentation to follicular helper T cells in the light zone is a key regulatory step.
• Showed a direct correlation between antigen load and the extent of B cell expansion and diversification.

Conclusions:

• The extent of B cell clonal expansion and immunoglobulin gene hypermutation in germinal centers is regulated by antigen.
• Antigen capture and presentation by GC B cells to follicular helper T cells control B cell division and diversification.
• This mechanism ensures the selective expansion and diversification of high-affinity B cells during immune responses.