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Role of CD30 in B/T Segregation in the Spleen¹

Vasileios Bekiaris^2,*, David Withers^2,*, Stephanie H. Glanville^2,*, Fiona M. McConnell^2,*, Sonia M. Parnell^3,*, Mi-Yeon Kim^3,*, Fabrina M. C. Gaspal^3,*, Eric Jenkinson^3,*, Clive Sweet^3,, Graham Anderson^3,* and Peter J. L. Lane^2,4,*

^* Medical Research Council Centre for Immune Regulation, Birmingham Medical School; and School of Biosciences, Birmingham, United Kingdom

In this report, we identify an important function for CD30 signals in the effective segregation of B and T lymphocytes in the murine spleen, additional to the recognized requirement for lymphotoxin signals. We show that CD30 signals are not required for transcription or protein expression of homeostatic chemokines, but CD30-deficient mice display impaired B/T segregation. This defect correlates with defective expression as detected by Abs of the transmembrane mucin-type protein podoplanin on T zone stroma, although expression at other sites is normal. Defective segregation is not intrinsic to CD30-deficient lymphocytes which segregate normally following transfer into RAG-deficient mice and significantly up-regulate the expression of both CCL21 and podoplanin on T zone stroma of RAG-deficient mice. During development, induction of expression of the CD30 ligand by lymphoid tissue inducer cells and podoplanin by T zone stroma are temporally linked, and the spatial association of these cells suggests that lymphoid tissue inducer cells are capable of providing the CD30 signals. Finally, we show that the appearance of podoplanin on T zone stroma in development is associated with B/T segregation of splenic white pulp areas. Our studies indicate that homeostatic chemokine expression by itself is not sufficient for B/T segregation and our data point to a significant role for podoplanin or molecules associated with podoplanin expressing stroma in the effective segregation of lymphocytes.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by a Wellcome Programme Grant to P.L. and G.A.

² V.B., D.W., F.M.M., S.H.G., and P.J.L.L. designed and performed the research, collected and analyzed the data, and wrote the article.

³ S.M.P., M.-Y.K., F.M.C.G., E.J., C.S., and G.A. contributed to designing and performing the research.

⁴ Address correspondence and reprint requests to Dr. Peter J. L. Lane, Medical Research Council Centre for Immune Regulation, Institute for Biomedical Research, Birmingham Medical School, Birmingham B15 2TT, U.K. E-mail address: p.j.l.lane{at}bham.ac.uk

⁵ Abbreviations used in this paper: LTβR, lymphotoxin β receptor; LTI, lymphoid tissue inducer; LT, lymphotoxin; WT, wild type; DC, dendritic cell; TRITC, tetramethylrhodamine isothiocyanate; Ct, cycle threshold.

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				V. Bekiaris, O. Timoshenko, T. Z. Hou, K. Toellner, S. Shakib, F. Gaspal, F. M. McConnell, S. M. Parnell, D. Withers, C. D. Buckley, et al. Ly49H+ NK Cells Migrate to and Protect Splenic White Pulp Stroma from Murine Cytomegalovirus Infection J. Immunol., May 15, 2008; 180(10): 6768 - 6776. [Abstract] [Full Text] [PDF]