T cells and natural killer cells regulate human IgG subclass concentrations in SCID mice

Cytokine regulation of human IgG subclass production is not well understood. Since T cells and natural killer (NK) cells produce IL-4 and/or IFN-gamma, we examined the effect of these cells on human IgG subclass concentration in reconstituted severe combined immunodeficient (SCID) mice. SCID mice receiving only B-cell-enriched splenocyte preparations had significantly decreased IgG concentrations and significantly decreased IgG1/IgG2 ratios compared to mice receiving B cells plus T cells (P = 0.02). IgG2 represented 58% of the total IgG at 28 days in mice receiving B-cell-enriched preparations compared to 19% of the total for the group receiving both B cells and T cells (P = 0.013). The effect of natural killer cells (CD16+) on IgG subclass was also studied in this model. IgG2 concentrations were twofold higher in mice receiving CD16-depleted cells compared to controls (P = 0.004). No significant differences were noted for IgG1, IgG3, or IgG4 subclass concentrations. In conclusion, T cells and natural killer cells influence human IgG subclass regulation in the SCID mouse model. We propose that the regulation of human IgG subclass production can be further examined in the SCID model.