We wish to test the hypothesis that the development of B cell lymphomas in humans represents a multistep process which begins in the bone marrow. This idea stemmed from studies of B and T cell malignancies in chickens and mice, and we have obtained support for it in previous studies of humans with pre-B, B and plasma cell malignancies. It contrasts with the prevailing view that B cell lymphomas arise in the lymph node; the nodular lymphomas having as their origin a subpopulation of target cells in germinal centers. In the present studies we will examine the extent of clonal involvement in patients with nodular B cell lymphomas. Cell hybridization techniques will be used to produce two types of monoclonal anti-idiotype (Id) antibodies: One specific for idiotypic determinants expressed by complete immunoglobulin molecules and others specific for V(H) idiotopes expressed on the isolated Mu heavy chains made by the B lymphoma. The former will be used to trace the distribution of the B cells belonging to the neoplastic clone in lymph node, blood and bone marrow tissue samples. The anti-V(H) Id will be used to search for members of the neoplastic clones among the pre-B cell population in the bone marrow. After determining the extent of clonal involvement, neoplastic cells and normal B cells will be isolated from each of the involved tissues and pre-B cells isolated from bone marrow. These subpopulations of cells will then be separately examined by cytogenetic techniques for chromosomal abnormalities, and restriction fragments of the cellular DNA will be analyzed with heavy and light chain gene cDNA probes to determine immunoglobulin gene rearrangements and clonality. Other studies will address the expression of cellular oncogenes in the different subpopulations. In this way we hope to learn more about the origin and the steps involved in the development of B cell lymphomas.
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