Immunoglobulins are expressed as membrane-bound or secreted forms. Plasma cells produce little or no membrane
immunoglobulin but secrete
immunoglobulin molecules in large amounts.
Immunoglobulin idiotypes of malignant B cells are
tumor-specific
antigens that may be targeted for
immunotherapy. Thus, idiotype vaccination is being evaluated in clinical trials to control residual disease in
multiple myeloma and
non-Hodgkin's lymphoma. It is traditionally considered that
anti-idiotype antibodies are not effective against
plasma cell tumors, because the large amounts of
immunoglobulin molecules secreted by the
tumors block
anti-idiotype antibodies, and because the absence of membrane
immunoglobulin on the surface of these
tumor cells renders them resistant to the effect of
anti-idiotype antibodies. While the obstacle of abundant circulating idiotype may be obviated by reducing
tumor burden to
minimal residual disease, the absence of membrane
immunoglobulin has been considered as a limiting factor that prevents
tumor eradication by
anti-idiotype antibodies. We demonstrate here that murine
plasmacytoma cells can produce small amounts of membrane
immunoglobulin M (
IgM) heavy chains. However, the latter are precursor molecules that do not reach the cell surface. Although membrane-bound
IgM is absent, the cells
stain positively for surface
IgM, reflecting molecules of the secreted form in the process of secretion. In spite of the relatively low levels of secreted
immunoglobulin on the cell surface,
anti-idiotype antibodies are effective in retardation of
tumor growth in vivo. Thus, while there is no doubt that idiotype-specific cell-mediated responses are very important, myeloma patients
in complete remission may additionally benefit from idiotype-specific humoral responses.