Promotion of T Regulatory Cells in Mice by B Cells and BAFF

In addition to promoting B cell expansion, overexpression of BAFF promotes expansion of T cells, including T regulatory (Treg) cells. To determine the relationships among BAFF, B cells, and Treg cells, a panel of C57BL/6 (B6) congenic mice was tested. Treg cells were disproportionately expanded in mice expressing a Baff transgene (B6.BTg) and were disproportionately contracted in mice deficient in BAFF (B6.Baff ). In vitro suppressor activities of B6 wild-type, B6.BTg, and B6.Baff Treg cells were identical, as was in vitro generation of Treg cells. In vivo proliferation of Treg cells was greatest in B6.BTg mice, whereas in vivo survival of Treg cells was lowest in B6.Baff mice. B cells promoted BAFF-independent Treg cell expansion in vivo, as evidenced by the correlation between B cells and percentages of Treg cells in B6.Baff mice and by the greater percentages of Treg cells in B6.Bcl2 mice (which harbor B cells largely independent of BAFF because of expression of a Bcl2 transgene) than in B6 wild-type mice despite the lower serum BAFF levels in the former than in the latter. Experiments with BAFF-deficient B6.Baff Bcl2 mice, B cell-deficient B6.μMT mice, BAFF-overexpressing/B cell-deficient B6.BTg.μMT mice, and BAFF-deficient/B cell-deficient B6.Baff μMT mice demonstrated that, in a host that harbors B cells, the effect of BAFF on Treg cells goes beyond its ability to expand the B cell population and is additional to the BAFF-independent effect of B cells on Treg cells. These findings may have considerable relevance to the treatment of B cell-associated autoimmune diseases.