Ectopic B-cell clusters that infiltrate transplanted human kidneys are clonal

Area of Science:

• Immunology
• Transplantation
• Molecular Biology

Background:

• B cells and their immunoglobulin products are implicated in allograft rejection.
• Germinal center-like B-cell clusters are observed in transplanted human kidneys.

Purpose of the Study:

• To investigate the immunoglobulin repertoires of B cells infiltrating kidney allografts.
• To determine the clonality and gene usage of these infiltrating B cells.

Main Methods:

• Construction and analysis of antibody libraries from infiltrating B cells.
• Comparison of immunoglobulin gene expression in kidney allografts versus peripheral blood.

Main Results:

• Infiltrating B cells in kidney allografts exhibit highly restricted immunoglobulin repertoires.
• B cells within clusters are clonal, with each patient showing dominant germline gene and CDR3 usage.
• Dominant clones in kidney allografts differ from those in peripheral blood.

Conclusions:

• Kidney allograft infiltrating B cells display characteristics of highly activated lymphocytes, including somatic recombination machinery.
• The findings suggest a potential link between chronic antigenic drive in allografts and the emergence of dominant B-cell clones, potentially leading to lymphoid malignancy.