PHENOTYPES IN CHRONIC B-LYMPHOCYTIC LEUKEMIA PROBED BY MONOCLONAL-ANTIBODIES AND IMMUNOGLOBULIN SECRETION STUDIES - IDENTIFICATION OF STAGES OF MATURATION ARREST AND THE RELATION TO CLINICAL FINDINGS

  • 1 January 1983
    • journal article
    • research article
    • Vol. 62  (4) , 910-917
Abstract
Neoplastic populations from 25 [human] cases of B-lymphocytic leukemia (B-LL) were investigated in an attempt to define the stages of maturation arrest represented in this disease and the relationship, if any, to various clinical parameters. Intrinsic to the study was the expression of a number of B-cell antigens defined by monclonal antibodies. These included antibodies to B1 and B2, both expressed exclusively on B lymphocytes, but with the latter probably restricted to a narrow window of differentiation, BB-1 and LB-1, both markers of activated lymphocytes, and 38.13, a monoclonal antibody raised against and recognizing an epitope expressed on Burkitt lymphoma cells. While the patterns of reactivities were complex, the cases could be classified into various groups on the basis of the phenotypes revealed. These were termed pre-B, early-B, intermediate-B, mature-B and secretory-B from their patterns of Ig isotype expression and their capacity to secrete Ig in short-term culture. Although B1 was detected on neoplastic cells from all but 1 case, its intensity of expression varied markedly, being strongest on the mature-B and secretory-B cases and weakest on the pre-B type. The expression of B2 was essentially restricted to the intermediate-B, mature-B and secretory-B cases and was usually, but not invariably, accompanied by the coexpression of surface IgM and IgD. While expression of BB-1 was restricted to a few cases with mature features, LB-1 was more frequently detected and found predominantly on intermediate B and mature B cases. The 38.13 antibody reacted weakly with a number of the populations coexpressing IgM and IgD. The export of large amounts of whole Ig was restricted to 3 secretory-B cases all of which were associated with a serum M-component corresponding to the Ig isotype secreted in vitro. Secretion of free Ig light chains was a consistent feature of all B-LL, and the amounts detected did not vary considerably between the different types. No correlation between immunologic cell-type and the stage of the disease was apparent. Classification of ther cases into true B-chronic lymphocytic leukemia and immunocytoma similarly revealed no strict association of these histopathologic entities with any particular phenotypic group, although those cases with the more mature features tended to be immunocytomas. Findings are discussed within the context of normal B-cell differentiation pathways.