Introduction. The 564Igi mouse is a murine model of SLE, generated by knock-in of a B cell receptor of an autoreactive B-cell clone. Characterization of mixed BM chimeras (of 564Igi and wild-type (WT) mice) demonstrate that WT B-cells acquired new targets of auto-reactivity, became self-sustained and gained independence from the initial trigger (ARTEMIS model). We now further progress on these findings by utilizing the parabiosis model, in which 564Igi and WT mice are surgically joined and lymphocytes can subsequently freely exchange between the mice without the initial lymphopenia and need for irradiation as in the ARTEMIS model.
Results. An exchange of B- and T cells could already be noticed as early as 6 days post-surgery. After 2 weeks half of the B- and T-cells in the 564Igi mouse were of WT origin (n=6). At this point the mice were separated but circulating WT B-cells remained at a stable level for several weeks post-separation while WT T-cells gradually decreased (n=4). In the germinal center (GC), the majority (~80%) of B-cells were WT, while ~20% of T-cells. To test whether WT B-cells are actively engaged in the GC process, we transferred splenocytes of AID-Cre-Ert2-eYFP mice into 564Igi and WT mice. YFP expression in the 564Igi mouse was evident in WT GC B-cells (15%, n=3), but almost absent in B6 (0.6%, n=4) mice, indicating active GC participation of WT B-cells in 564Igi mice.
Conclusion. The 564Igi murine model of SLE supports the maintenance and active participation of WT B-cells in the germinal center.