Murine complement-mediated immune clearance dysfunction is associated with the lymphoproliferative (lpr) gene

Area of Science:

• Immunology
• Genetics
• Pharmacology

Background:

• Autoimmune MRL-lpr/lpr mice exhibit abnormal in vivo clearance of opsonized erythrocytes.
• A branched series model quantifies immune clearance via complement and Fc gamma receptor pathways.

Purpose of the Study:

• To investigate genetic factors contributing to abnormal erythrocyte clearance in MRL-lpr/lpr mice.
• To assess the impact of the lymphoproliferative gene on immune clearance mechanisms.

Main Methods:

• Utilized a branched series model and iterative curve fitting to evaluate four rate constants (k1-k4) of immune clearance.
• Conducted serial clearance studies in MRL-(+/+) mice and lymphoproliferative gene-homozygous strains (BALB/c-lpr/lpr, C57BL/6-lpr/lpr) across various ages.
• Compared rate constant values to control mouse strains (BALB/c, C57BL/6).

Main Results:

• MRL-lpr/lpr mice showed impaired complement and Fc gamma receptor function, with decreased sequestration and phagocytosis.
• Congenic MRL-(+/+) mice displayed only decreased Fc gamma-mediated clearance.
• BALB/c-lpr/lpr and C57BL/6-lpr/lpr mice exhibited significantly reduced complement-mediated clearance, similar to MRL-lpr/lpr mice.

Conclusions:

• Immune clearance of opsonized cells in mice is partly genetically determined.
• A specific association exists between complement-mediated clearance dysfunction and the murine lymphoproliferative gene.
• The lymphoproliferative gene may play a role in impaired complement-mediated clearance observed across different mouse strains.