Replacing mouse BAFF with human BAFF does not improve B-cell maturation in hematopoietic humanized mice

Area of Science:

• Immunology
• Genetics
• In vivo modeling

Background:

• Hematopoietic humanized mice (hu-mice) model the human immune system.
• Impaired human B-cell maturation in hu-mice may stem from poor interaction between human B-cell-activating factor (hBAFF) receptor and mouse B-cell-activating factor (mBAFF).

Purpose of the Study:

• To investigate if replacing mouse BAFF with human BAFF improves human B-cell maturation in hu-mice.
• To determine if mBAFF bioactivity limits human B-cell development.

Main Methods:

• Created a genetically engineered mouse strain replacing the mBAFF gene with human BAFF cDNA.
• Analyzed B-cell populations, immunoglobulin levels, and antibody responses in hBAFF knock-in (hBAFFKI) hu-mice.

Main Results:

• hBAFF expression did not increase mature human B cells in hu-mice.
• hBAFFKI hu-mice showed proportionally more immature B cells and reduced memory B cells, plasmablasts, and plasma cells.
• Diminished immunoglobulin G levels and T-cell-independent antibody responses were observed.

Conclusions:

• Inefficient B-cell maturation in hu-mice is not caused by suboptimal mBAFF bioactivity on human B cells.
• The hypothesis that mBAFF interaction limits human B-cell maturation was not supported.