Recently B cells with immunoregulatory properties have been found in mice but evidence for a potential role in humans remains elusive. We have identified a population of highly activated human B cells with regulatory properties in vitro which could induce temporary anergy and apoptosis in Th cells. Now we intend to test the role of such "Breg" cells in human autoimmune SLE. Methods: CD19+B and CD4+Th cells were separated from PBMC of healthy (ND) or SLE donors by MACS-sorting. B cells were prestimulated with SAC for 3d and sorted into highly activated FSChiCD25+ (lgB25+) and small resting FSCloCD25- (smB25-) B cells by FACS. Upon 4d coculture with Th cells and αCD3+IL-2, T cell growth was determined by 3H-TdR incorporation. Results: less inhibition of T cell growth by lgB25+SLE-B (60% of proliferation of T cells alone) was observed compared to lgB25+ND-B (35% of proliferation of T cells alone), independent of T-cell origin: ND-T cell proliferation decreased below 50% of controls in 11 of 12 cases with lgB25+ND-B, in contrast to only 5 of 12 cases with lgB25+SLE-B. No significant difference in cell viability or expression of CD80, CD86, B7-H1, GITR or CD27 could be found between both B-cell populations. We conclude that lgB25+B from SLE patients are less effective in control of Th-cells in vitro. Future experiments deal with the mechanisms, potential correlations with treatment or disease stage, and relevance for pathogenesis of autoimmunity.