Tim-1 is induced on germinal centre B cells through B-cell receptor signalling but is not essential for the germinal centre response.
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.
MRC Laboratory of Molecular Biology, Cambridge, UK. shwong@mrc-lmb.cam.ac.uk
See Heng
SH
Wong
Jillian L
JL
Barlow
Stephen
S
Nabarro
Padraic G
PG
Fallon
Andrew N J
AN
McKenzie
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018858:Germinal Center / Q000276:immunology* / Q000378:metabolism; D000072596:Hepatitis A Virus Cellular Receptor 1; D008213:Lymphocyte Activation / Q000276:immunology*; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D015398:Signal Transduction
C442240:Havcr1 protein, mouse; D000072596:Hepatitis A Virus Cellular Receptor 1; D008565:Membrane Proteins; D016328:NF-kappa B; D011947:Receptors, Antigen, B-Cell; D019869:Phosphatidylinositol 3-Kinases