Stromal cell-derived factor-1 as a chemoattractant for follicular center lymphoma B cells.
BACKGROUND
Follicular center lymphoma displays widespread lymph node involvement at diagnosis. The chemoattractants that control the locomotion of follicular center lymphoma B cells have not been established. Stromal cell-derived factor-1 (SDF-1) is a CXC-class chemokine that enhances the migration of normal human B cells and is expressed in peripheral lymphoid tissues. Here we have investigated 1) whether SDF-1 stimulates the in vitro locomotion of follicular center lymphoma B cells and of their presumed normal counterparts (i. e., germinal center B cells) and 2) whether the same cells express SDF-1 transcripts.


METHODS
B cells were purified by immunomagnetic bead manipulation. Messenger RNA was detected by reverse transcription-polymerase chain reaction. Migration was assessed by the filter and collagen invasion assays. All P values were two sided.


RESULTS
Follicular center lymphoma B lymphocytes showed a statistically significant migratory response to 300 ng/mL SDF-1, both in the filter and in the collagen assays (P =.002 for each). Such response was mediated by the SDF-1 receptor, CXCR4. CD40 monoclonal antibody (MAb) and tonsillar germinal center B cells treated with CD40 MAb and recombinant interleukin 4, but not freshly isolated, migrated statistically significantly faster in the presence than in the absence of SDF-1 (P =.002 in both filter and collagen assays). Freshly isolated follicular center lymphoma and germinal center B cells expressed SDF-1 transcripts.


CONCLUSIONS
This study shows that SDF-1 substantially enhances the migration of follicular center lymphoma B cells but not the migration of freshly purified germinal center B cells. This difference may be related to the extended survival of follicular center lymphoma versus germinal center B cells. SDF-1 produced in follicular center lymphoma lymph nodes may play a role in the local dissemination of tumor cells.
Corcione
A
A
Laboratory of Oncology, G. Gaslini Institute, Genoa, Italy. laboncologia@ospedale-gaslini.ge.it
Ottonello
L
L
Tortolina
G
G
Facchetti
P
P
Airoldi
I
I
Guglielmino
R
R
Dadati
P
P
Truini
M
M
Sozzani
S
S
Dallegri
F
F
Pistoia
V
V
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001402:B-Lymphocytes / Q000378:metabolism / Q000502:physiology*; D001483:Base Sequence; D019013:CD40 Antigens / Q000276:immunology / Q000502:physiology; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000235:genetics / Q000494:pharmacology*; D002630:Chemotactic Factors / Q000494:pharmacology*; D002633:Chemotaxis; D015870:Gene Expression; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism; D008224:Lymphoma, Follicular / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D019718:Receptors, CXCR4 / Q000378:metabolism; D019948:Receptors, Interleukin-4 / Q000276:immunology / Q000502:physiology
D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D019718:Receptors, CXCR4; D019948:Receptors, Interleukin-4