Control of B-cell responses by Toll-like receptors

Nature, 438:364-368 (2005)

Speaker: 林士超                            Time: Mar. 22 2005, 13:10-14:00

Commentator: 陳舜華 老師                   Place: Room 601

Abstract:

Toll-like receptors (TLRs) are a kind of pathogen pattern-recognition receptors of the innate immunity and control the initiation of adaptive immune responses. However, the mechanisms of TLRs affect  adaptive immunity are not well-known. The authors investigate how TLRs control the B-cell responses, including antibody production, antigen processing, presentation, and differentiation by means of MyD88 knockout mice. MyD88, myeloid differentiation primary response gene 88, is an adaptor within TLR-mediated signaling transduction. MyD88^-/- mice can neither induction of normal antibody production nor T_H1 cytokine secretion, such as IFN-γ (1). They found that B cells can not be induction of T-dependent antibody responses without TLR signaling even though under the help of activated T_H cells after regulatory T cells (T_R) are depleted (2). After transferring the B cells from MyD88^-/- mice to μMT mice, which lack normal population of B cells, IgM and IgG1 production is abolished suggested that TLR signaling is not only related to antibody production but also isotype switch. In addition, it is also discovered that TLR signaling can contribute to germinal center formation though up-regulation of BCL-6 and reduction of Blimp-1 expression. BCL-6 and Blimp1 are the master regulators of the germinal centre to plasma cell transition. As a result, B cells can’t differentiate into antibody-producing plasma cells in MyD88^-/- mice. In conclusion, T-cell activation is insufficient for T-dependent B-cell responses and TLR-mediated signal pathway plays a critical role in both of innate and adaptive immunity.

References:

1. Schnare, M. et al. Toll-like receptors control activation of adaptive immune responses. Nat. Immunol. 2:947–-950 (2001).

2. Pasare, C. and Medzhitov, R. Toll-dependent control mechanisms of CD4 T cell activation. Immunity 21:733–-741 (2004).

3. Pasare C. and Medzhitov, R. Control of B-cell responses by Toll-like receptors. Nature, 438:364-368 (2005).