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

Immunology. 2010 Sep;131(1):77-88. doi: 10.1111/j.1365-2567.2010.03276.x. Epub 2010 May 26.

Abstract

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-kappaB 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Germinal Center / immunology*
  • Germinal Center / metabolism
  • Hepatitis A Virus Cellular Receptor 1
  • Lymphocyte Activation / immunology*
  • Membrane Proteins / deficiency
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • NF-kappa B / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Receptors, Antigen, B-Cell / metabolism*
  • Signal Transduction*

Substances

  • Havcr1 protein, mouse
  • Hepatitis A Virus Cellular Receptor 1
  • Membrane Proteins
  • NF-kappa B
  • Receptors, Antigen, B-Cell
  • Phosphatidylinositol 3-Kinases