Research Project
Grant-in-Aid for Young Scientists (A)
We focused on CD69 which is known as an activation marker, because resting memory T helper cells expressed it in the bone marrow and clarified the essential role of CD69 in relocation of splenic effector T helper cells to the bone marrow by using CD69-deficient mice which our laboratory generated. Moreover, we also found the sufficient role of CD49b, also called as integrin alpha2, in their relocation by using CD49b-deficient mice (in revision). These data suggest that effector T helper cells expressing both CD69 and CD49b from the secondary lymphoid organs relocate to the bone marrow by a two-step process.To examine roles of bone marrow memory T helper cells, we evaluated humoral immune response of CD69-deficient mice which lacks them. CD69-deficient mice have a marked reduction of production of high-affinity antibodies and generation of long-lived plasma cells in the bone marrow, although they normally produced antibodies and generate splenic plasmablasts in the early phase of an immune response. The reduction was due to a defective help of bone marrow memory T helper cells for homing of plasmablasts to the bone marrow. Since this helper function is antigen-dependent, the data suggests a fact of T-B interaction via T-cell receptor/MHC class II. Since CD69-deficient mice can normally generate follicular helper T cells and germinal center B cells, this help for B lineages is a novel role of bone marrow memory T helper cells after germinal center reaction. We are identifying the essential candidates for this T-cell help and the studies will contribute the understanding of T helper cell memory.
All 2012 2011 2010
All Journal Article (7 results) (of which Peer Reviewed: 7 results) Presentation (22 results)
Proc.Natl.Acad.Sci.USA
Volume: (in press) Issue: 19 Pages: 7409-7414
10.1073/pnas.1118539109
Cell. Mol. Life Sci.
Volume: 69 Issue: 10 Pages: 1609-1613
10.1007/s00018-012-0969-6
Immunity
Volume: 35 Issue: 5 Pages: 733-745
10.1016/j.immuni.2011.08.017
J. Allergy Ciln. Immunol
Volume: 128 Pages: 1067-1076
Volume: 128 Issue: 5 Pages: 1067-1076
10.1016/j.jaci.2011.06.018
Eur. J. Immunol
Volume: 40 Issue: 11 Pages: 2993-3006
10.1002/eji.201040936
European Journal of Immunology
Volume: 40 Pages: 2993-3006