The Impact of T Helper and T Regulatory Cells on the Regulation of Anti-Double-Stranded DNA B Cells

Autoreactive B cells that appear to be inactivated can be found in healthy individuals. In this study, we examined the potential of these anergic cells to become activated. We show that anergy of anti-double-stranded DNA (dsDNA) B cells in BALB/c mice is readily reversed, requiring only the provision of T cell help. We further show that spontaneous loss of anergy among anti-dsDNA B cells in autoimmune lpr/lpr mice occurs in two phases: an abortive initial response to T help followed by full loss of tolerance. Strikingly, the abortive response can be reproduced in nonautoimmune mice when CD4 +CD25 + T regulatory cells are administered in conjunction with CD4 + T helper cells, suggesting that loss of B cell tolerance may require both the production of T cell help and the overcoming of T suppression.