Biology of the neoplastic lymphocyte in B-CLL.

Immunological markers have identified the proliferating lymphocyte in CLL as a mature B lymphocyte which, unlike lymphocytes in other B cell malignancies, expresses low amounts of surface membrane immunoglobulin (smIg), forms rosettes with mouse erythrocytes and expresses the CD5 marker. It has been postulated that Ly1 B cells (the murine counterpart of human CD5+B cells) constitute a separate B cell lineage. Whether the CD5 marker defines a discrete lineage or is a maturation marker is one of the main issues that might be solved in the near future. Another recent advance has been the discovery that the B lymphocyte in CLL is in an activated state and can be induced to differentiate. Using B cell mitogens and somatic hybridization, it has been demonstrated that the B-CLL lymphocyte is frequently involved in the production of natural autoantibodies and expresses a restricted set of genes. These results may provide a basis for passive immunotherapy using anti-idiotypic antibodies. Hypogammaglobulinaemia is a distinct feature of B-CLL, observed in 60% of patients. It may result from impaired function of residual normal B cells. This could occur as a consequence of progressive dilution of normal non-clonal B cells, or because normal B cells are downregulated by an unknown mechanism. This decrease in or inhibition of normal CD5-B cells could also explain the classical inability of patients with B-CLL to respond to new antigenic challenges, since Ly1 B cells have been claimed to be unable to respond to exogenous antigens. Although regulatory abnormalities in T cells may play a role in the induction of hypogammaglobulinaemia, data concerning helper, suppressive, NK and ADCC cells are contradictory and fail to establish firmly the contribution of these cells in the development of hypogammaglobulinaemia. Associated autoimmune phenomena are a prominent complication in CLL. They are related to the presence of autoantibodies directed mainly against blood components, which in most cases are not the product of the malignant clone. The relationship between autoimmune phenomena and hypogammaglobulinaemia is not definitively substantiated. That hypogammaglobulinaemia may determine the loss of some anti-idiotypic antibodies designed to antagonize autoimmune clones is an attractive hypothesis, which needs to be substantiated. Several recurrent chromosomal abnormalities, such as trisomy 12, structural aberrations of the 13q14 and 14q32 bands, are frequently observed in B-CLL. Less frequently, alterations of chromosomes 11, 6, 18, 3, 17, 7 and 8 have been reported.(ABSTRACT TRUNCATED AT 400 WORDS)