Toll-like receptor 4-activated B cells out-compete Toll-like receptor 9-activated B cells to establish peripheral immunological tolerance

作者：Matheu Melanie P; Su Yan; Greenberg Milton L; Blanc Caroline A; Parker Ian; Scott David W^*; Cahalan Michael D

来源：Proceedings of the National Academy of Sciences, 2012, 109(20): E1258-E1266.

DOI：10.1073/pnas.1205150109

• immunoimaging
• lymph node

B-cell-induced peripheral T-cell tolerance is characterized by suppression of T-cell proliferation and T-cell-dependent antibody production. However, the cellular interactions that underlie tolerance induction have not been identified. Using two-photon microscopy of lymph nodes we show that tolerogenic LPS-activated membrane-bound ovalbumin (mOVA) B cells (LPS B cells) establish long-lived, highly motile conjugate pairs with responding antigen-specific OTII T cells but not with antigen-irrelevant T cells. Treatment with anti-CTLA-4 disrupts persistent B-cell-T-cell (B-T) contacts and suppresses antigen-specific tolerance. Nontolerogenic CpG-activated mOVA B cells (CpG B cells) also form prolonged, motile conjugates with responding OTII T cells when transferred separately. However, when both tolerogenic and nontolerogenic B-cell populations are present, LPS B cells suppress long-lived CpG B-OTII T-cell interactions and exhibit tolerogenic dominance. Contact of LPS B cells with previously established B-T pairs resulted in partner-swapping events in which LPS B cells preferentially migrate toward and disrupt nontolerogenic CpG mOVA B-cell-OTII T-cell pairs. Our results demonstrate that establishment of peripheral T-cell tolerance involves physical engagement of B cells with the responding T-cell population, acting in a directed and competitive manner to alter the functional outcome of B-T interactions.

• 出版日期2012-5-15