Analysis of epitope expression and the functional repertoire of recombinant complement receptor 2 (CR2/CD21) in mouse and human cells.

Boosting B Cell Responses

CR2 partners with CD19 to form a co-receptor complex that amplifies B cell receptor (BCR) signals. Mice lacking CR2 show impaired antibody responses, highlighting its role in adaptive immunity .

Viral Hijacking: The EBV Connection

EBV exploits CR2 to infect B cells. Transfecting mouse cells with human CR2 restores EBV binding, but infection rates differ between species—hinting at additional host factors .

Autoimmunity: When CR2 Goes Rogue

• Lupus: CR2 binds IFN-α, a cytokine overproduced in lupus. Blocking CR2 in B cells reduces IFN-α-driven gene expression, suggesting therapeutic potential .
• Atopic Dermatitis (AD): Lower CR2 levels in AD patients correlate with dysregulated immune responses .

Table 2: CR2 in Disease Models

Model	Finding	Implication
CR2−/− mice	Defective antibody responses	Validates CR2’s role in immunity
Humanized mice	Human CR2 restores B cell function	Supports cross-species studies

Recombinant CR2: Lessons from Mouse and Human Cells

Species-Specific Surprises

• Human CR2 in Mouse Cells: Restores complement and EBV receptor functions but with lower EBV infection efficiency, suggesting post-binding mechanisms differ .
• Expression Regulation: CR2 is absent in pre-B cells but induced by IL-4 and CD40 signaling in mature B cells—key for vaccine design .

Table 3: Recombinant CR2 Studies

Study	Key Insight	Technique
Carel et al. (1989)	CR2 alone enables C3d/EBV binding in heterologous cells	Flow cytometry, immunoprecipitation
Marchbank et al. (2000)	Human CR2 rescues immune function in CR2−/− mice	Transgenic models

Therapeutic Horizons: Targeting CR2’s Dual Nature

Monoclonal Antibodies (mAbs):

• mAb 171 blocks the CR2-C3d interface, inhibiting EBV and lupus pathways .

CR2-Targeted Inhibitors:

• Engineered CR2 fragments compete for ligand binding, reducing inflammation in lupus models .

Gene Therapy:

• Restoring CR2 expression in B cells could counteract immunodeficiency.

Conclusion: The Future of CR2 Research

CR2/CD21 is a linchpin in immunity, offering both vulnerabilities and therapeutic opportunities. From its structural intricacies to its role in diseases, recombinant studies continue to illuminate its potential. As researchers unravel species-specific quirks and design smarter inhibitors, CR2 stands poised to revolutionize treatments for infections, autoimmune disorders, and beyond.