Unconjugated
Advances in flow cytometry techniques and the availability of monoclonal antibodies that detect key functional molecules on lymphocytes have contributed greatly to a more precise diagnosis of the chronic lymphoproliferative disorders. In addition to the diagnostic value, the expression of certain markers such as p53 or CD38 provides relevant prognostic information to the clinician. Beyond their diagnostic and prognostic value, immunological markers play a major role in the detection of minimal residual disease, enabling the clinician to estimate more accurately the response to chemotherapy. Those monoclonal antibodies that are relevant to the characterisation of the chronic lymphoproliferative disorders and that could be incorporated in a routine practice are discussed.
Two covalently linked transmembrane molecules, encoded in mice by the mb-1 and B29 genes, have been defined as integral components of the antibody receptor units expressed on B cells. We have produced monoclonal antibodies against an exposed extracellular epitope on the putative human equivalent of the mouse B29 product. These antibodies, CB3-1 and -2, were used to show that cytoplasmic expression of this molecule begins in human pro-B cells (terminal deoxynucleotidyltransferase-positive, mu chain-negative), whereas surface expression coincides strictly with surface immunoglobulin expression of all isotypes. Immunochemical analysis of the human immunoglobulin-associated molecules revealed greater molecular heterogeneity than has been noted for the murine analogues. This molecular heterogeneity of immunoglobulin-associated molecules varied as a function of differentiation stage and the immunoglobulin isotypes expressed by B-lineage cells. Our data support the hypothesis that biochemical heterogeneity of the surface immunoglobulin-associated molecules may contribute to the variability in biological effects of antigen receptor crosslinkage on B cells of different maturational stages. Because the CB3 antibodies are capable of down-modulating the antigen receptors on all B cells, they may prove therapeutically useful as universal B-cell suppressants.