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Membrane
CD22 Defines Circulating Myeloma-Related Cells as Mature or Later B Cells |
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Vittorio Perfetti,
Maurizio Colli Vignarelli, Vittorio Bellotti, Martin J. Glennie, Irene Zorzoli,
Paola Ubbiali, Laura Obici, Margherita Massa, Giovanbattista Ippoliti, Edoardo
Ascari, and Giampaolo Merlini |
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Research
Laboratories of Biotechnology (MCV, PU, MM, GM) and Organ Transplantation,
Clinical Immunology Unit (VP), Internal Medicine and Medical Oncology (IZ,
LO, GI, EA), and Institute of Biochemistry (VB), University of Pavia-IRCCS
Policlinico S. Matteo, Pavia, Italy; and Lymphoma Research Unit (MJG), Tenovus
Research Laboratory, Southampton General Hospital, Southampton, United Kingdom
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Circulating clonally related
earlier cells are present in multiple myeloma (MM) and may be involved in
the dissemination of this disease, its recurrence, and chemoresistance.
The nature, stage of differentiation, and size of this cell population remain
uncertain. Unlike other B-cell markers, CD22 membrane expression is limited
to the late differentiation stages comprised between mature B cells (CD22+)
and plasma cells (PC; CD22-) and may thus be useful in delimiting the maturational
state of circulating early myeloma cells. Peripheral blood clone-related
cells were detected by anti-idiotypic (Id) monoclonal antibodies and found
to express CD22 (92% to 95%), monotypic light and heavy chain (100%), and
CD38 (45%), whereas bone marrow PC were CD22-negative. CD22 expression was
also documented on functional myeloma PC precursors, defined as peripheral
blood cells capable of in vitro cytokine-driven monotypic PC differentiation,
because up to approximately 70% inhibition of this process was obtained
in 10 myeloma patients through the use of bispecific antibodies (BsAb) that
deliver the plant toxin saporin to CD22+ cells. As further evidence of CD22
on circulating abnormal cells, it was found that in the only patient analyzed
for DNA content, a portion of the peripheral blood CD22+ cells killed were
hyperdiploid. Collectively, these findings indicate that most peripheral
blood myeloma PC precursors are mature or later B cells presenting membrane
CD22. The pattern of CD22 expression suggests the existence in MM of a differentiation
process analogous to the normal antigenic response, in which CD22+ B cells
migrate to the bone marrow and lose CD22 with PC differentiation. In addition,
the sensitivity of myeloma PC precursors to the cytotoxic effects of the
anti-CD22 BsAb and the possibility of interfering with their differentiation
have potential therapeutic relevance. |
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