| First Author | Matheu MP | Year | 2012 |
| Journal | Proc Natl Acad Sci U S A | Volume | 109 |
| Issue | 20 | Pages | E1258-66 |
| PubMed ID | 22511718 | Mgi Jnum | J:184681 |
| Mgi Id | MGI:5426075 | Doi | 10.1073/pnas.1205150109 |
| Citation | Matheu MP, et al. (2012) Toll-like receptor 4-activated B cells out-compete Toll-like receptor 9-activated B cells to establish peripheral immunological tolerance. Proc Natl Acad Sci U S A 109(20):E1258-66 |
| abstractText | 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. |
