Tim‐1 is induced on germinal centre B cells through B‐cell receptor signalling but is not essential for the germinal centre response

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Abstract
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.