Most peripheral B cells in mice are ligand selected

Area of Science:

• Immunology
• Molecular Biology
• Genetics

Background:

• The immunoglobulin heavy chain (VH) gene repertoire is crucial for adaptive immunity.
• Understanding VH gene utilization in different B cell subsets provides insights into immune system development and selection processes.

Purpose of the Study:

• To analyze the VH gene repertoire of pre-B cells and various B cell subsets in conventional mice.
• To investigate the selection mechanisms governing VH gene usage during B cell development and peripheral B cell pool formation.

Main Methods:

• Analysis of amplified cDNA and genomic libraries.
• Sequencing and evaluation of VH genes from the J558 VH gene family.
• Comparison of VH gene utilization across different B cell populations (pre-B cells, long-lived mu + delta high B cells, Ly-1 B cells).

Main Results:

• Pre-B cells exhibit broad utilization of J558 VH genes, with some bias from B cell-autonomous selection.
• Mature peripheral B cells (long-lived mu + delta high and Ly-1 B cells) predominantly express small, overlapping sets of germline VH genes.
• This selective expression pattern in mature B cells differs from T cell-dependent memory B cell selection due to the absence of immunoglobulin class switching and somatic hypermutation.

Conclusions:

• VH gene recruitment into the long-lived peripheral B cell pool is likely mediated by positive selection driven by self and/or foreign antigens.
• The observed VH gene usage patterns highlight distinct selection pressures acting on developing versus mature B cells.
• Antigen-driven selection, independent of somatic hypermutation and class switching, plays a significant role in shaping the mature B cell repertoire.