Tim‐1 is induced on germinal centre B cells through B‐cell receptor signalling but is not essential for the germinal centre response
Summary T‐cell immunoglobulin mucin‐1 (Tim‐1) has been proposed to be an important T‐
cell immunoregulatory molecule since its expression on activated T cells was discovered. To
study the role of Tim‐1 on T cells in vitro and in vivo we generated both Tim‐1‐deficient mice
and several lines of Tim‐1 transgenic mice with Tim‐1 expression on either T cells, or B and
T cells. We demonstrate that neither deficiency nor over‐expression of Tim‐1 on B and T
cells results in modulation of their proliferation in vitro. More surprisingly, T helper type 2 …
cell immunoregulatory molecule since its expression on activated T cells was discovered. To
study the role of Tim‐1 on T cells in vitro and in vivo we generated both Tim‐1‐deficient mice
and several lines of Tim‐1 transgenic mice with Tim‐1 expression on either T cells, or B and
T cells. We demonstrate that neither deficiency nor over‐expression of Tim‐1 on B and T
cells results in modulation of their proliferation in vitro. More surprisingly, T helper type 2 …
Summary
T‐cell immunoglobulin mucin‐1 (Tim‐1) has been proposed to be an important T‐cell immunoregulatory molecule since its expression on activated T cells was discovered. To study the role of Tim‐1 on T cells in vitro and in vivo we generated both Tim‐1‐deficient mice and several lines of Tim‐1 transgenic mice with Tim‐1 expression on either T cells, or B and T cells. We demonstrate that neither deficiency nor over‐expression of Tim‐1 on B and T cells results in modulation of their proliferation in vitro. More surprisingly, T helper type 2 cells generated either from Tim‐1‐deficient mice or Tim‐1 transgenic mice did not show enhancement of interleukin‐4 (IL‐4), IL‐5 and IL‐10 production. Furthermore, using a Schistosoma mansoni egg challenge as a potent T helper type 2 response inducer we also show that Tim‐1 is not essential for T‐ and B‐cell responses in vivo. However, we observe induction of Tim‐1 on B cells following B‐cell receptor (BCR), but not Toll‐like receptor 4 stimulation in vitro. We show that the induction of Tim‐1 on B cells following BCR stimulation is phosphoinositide‐3 kinase and nuclear factor‐κB pathway dependent. More importantly, we conclude that Tim‐1 is predominantly expressed on germinal centre B cells in vivo although the percentage of germinal centre B cells in wild‐type and Tim‐1‐deficient mice is comparable. Identification of Tim‐1 as a marker for germinal centre B cells will contribute to the interpretation and future analysis of the effects of the anti‐Tim‐1 antibodies in vivo.
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