Role of CD30 in B/T segregation in the spleen.
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.
Bekiaris
Vasileios
V
Medical Research Council Centre for Immune Regulation, Birmingham Medical School, Birmingham, UK.
Withers
David
D
Glanville
Stephanie H
SH
McConnell
Fiona M
FM
Parnell
Sonia M
SM
Kim
Mi-Yeon
MY
Gaspal
Fabrina M C
FM
Jenkinson
Eric
E
Sweet
Clive
C
Anderson
Graham
G
Lane
Peter J L
PJ
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D053285:CD30 Ligand / Q000235:genetics / Q000276:immunology; D018925:Chemokines / Q000235:genetics / Q000276:immunology; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D017730:Ki-1 Antigen / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D018448:Models, Immunological; D008969:Molecular Sequence Data; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology; D000098853:Podoplanin
D053285:CD30 Ligand; D018925:Chemokines; D017730:Ki-1 Antigen; D008562:Membrane Glycoproteins; C490441:Pdpn protein, mouse; D000098853:Podoplanin