CD100/Plexin-B1 interactions sustain proliferation and survival of normal and leukemic CD5+ B lymphocytes.
Growth and survival of chronic B-cell tumors are favored by the malignant cell's capacity to respond to selected microenvironmental stimuli provided by nontumoral bystander cells. To investigate which mechanisms operate in these crosstalks and whether they are malignancy-related or reproduce the mechanisms used by normal B cells we have studied the expression and functional role of semaphorin CD100 (now called Sema4D) in chronic lymphocytic leukemia (CLL) cells and normal CD5+ B cells. We demonstrate here that (1) leukemic and normal CD5+ B lymphocytes uniformly express CD100; (2) the CD100 high-affinity receptor Plexin-B1 is expressed by bone marrow stromal cells, follicular dendritic cells, and activated T lymphocytes, and is thus available to CD100+ lymphocytes in different specific microenvironments; and (3) upon interaction between CD100 and Plexin-B1 both CLL and normal CD5+ B cells increase their proliferative activity and extend their life span. These findings establish that Plexin-B1 is an easily accessible receptor for CD100 within the immune system. The encounter of CD100+ leukemic cells with Plexin-B1 may promote the proliferation and survival of malignant cells. The crosstalk operated by the CD100/Plexin-B1 interaction is not malignancy related but reproduces a mechanism used by normal CD5+ B cells.
Granziero
Luisa
L
Department of Oncological Sciences, University of Torino, Institute for Cancer Research and Treatment (IRCC), Candiolo (TO) and Division of Clinical Immunology and Hematology, Ospedale Mauriziano Umberto I, Torino, Italy.
Circosta
Paola
P
Scielzo
Cristina
C
Frisaldi
Elisa
E
Stella
Stefania
S
Geuna
Massimo
M
Giordano
Silvia
S
Ghia
Paolo
P
Caligaris-Cappio
Federico
F
D000818:Animals; D015703:Antigens, CD; D018941:Antigens, CD19 / Q000032:analysis; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology; D019013:CD40 Antigens / Q000502:physiology; D023201:CD40 Ligand / Q000494:pharmacology; D018956:CD5 Antigens / Q000032:analysis; D002455:Cell Division; D002460:Cell Line; D002470:Cell Survival; D018076:DNA, Complementary / Q000235:genetics; D020566:Dendritic Cells, Follicular / Q000378:metabolism; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000473:pathology*; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D014411:Neoplastic Stem Cells / Q000276:immunology / Q000473:pathology*; D009419:Nerve Tissue Proteins; D014066:Palatine Tonsil / Q000166:cytology; D011956:Receptors, Cell Surface; D039961:Semaphorins; D017154:Stromal Cells / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D014162:Transfection
D015703:Antigens, CD; D018941:Antigens, CD19; C093224:CD100 antigen; D019013:CD40 Antigens; D018956:CD5 Antigens; D018076:DNA, Complementary; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C492119:PLXNB1 protein, human; C492118:Plxnb1 protein, mouse; D011956:Receptors, Cell Surface; D039961:Semaphorins; D023201:CD40 Ligand