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A model for human B-chronic lymphocytic leukemia in human/mouse radiation
chimera: evidence for tumor-mediated suppression of antibody production in
low-stage disease
A Shimoni, H Marcus, A Canaan, D Ergas, M David, A Berrebi and Y Reisner
Department of Immunology, The Weizmann Institute of Science, Rehovot,
Israel.
B-chronic lymphocytic leukemia (BCLL) is a lymphoproliferative disease that
is characterized by clonal expansion of CD5+ B cells. BCLL is associated
with secondary immunodeficiency and hypogammaglobulinemia. It has been
suggested that T-cell dysregulation may play a role in the
hypogammaglobulinemia and in the increased incidence of autoimmunity in
BCLL patients. We attempted to transfer human peripheral blood mononuclear
cells (PBMC) from BCLL patients in different stages of the disease into
immunodeficient mice. PBMC from BCLL patients in stage 0, stages I to II,
and stages III to IV were transplanted into the peritoneal cavity of
lethally irradiated Balb/c or beige/nude/Xid (BNX) mice radioprotected with
bone marrow (BM) from severe combined immunodeficiency (SCID) mice.
Different engraftment profiles were found in the chimeric mice 2 weeks
after transplantation of PBMC according to the disease stage of the BCLL
donors. Infusion of PBMC from donors in stage 0 led to marked engraftment
of human T cells, whereas the human tumor cells could hardly be detected.
In contrast, chimeric mice receiving PBMC from patients in stage III to IV
disease exhibited engraftment with a dominance of tumor cells, compared
with a miniscule level of T cells. The ability of the engrafted cells to
produce human Ig was also found to be correlated with the disease stage of
the donor, although all donors had the same magnitude of
hypogammaglobulinemia. Total human Ig production in the chimeric mice was
normal in mice receiving PBMC from donors in stage 0, whereas in chimeric
mice engrafted with PBMC from donors in stages III to IV almost no human
Igs could be detected. This differential reconstitution of antibody
production in the mouse model according to the stage of the patient's
disease will allow further studies on possible cellular interactions
between malignant and immune cells in BCLL.
Volume 89,
Issue 6,
pp. 2210-2218,
03/15/1997
Copyright © 1997 by The American Society of Hematology
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