Mature T-lymphocytes are usually identified by monoclonal antibody detection of CD-2 antigen and mature B-lymphocytes by demonstration of surface Ig (usually by flow cytometry methods). The earliest B-cell stages are now identified by nucleic acid probes demonstrating characteristic rearrangement of intracellular genes for each component part of the Ig receptor molecule heavy chains and kappa and lambda light chains. The genetic material necessary to construct one type of chain is located in one chromosome, but the genetic material for other types of chains is located on different chromosomes. Each type of chain is constructed separately and sequentially, finally being united to form the Ig receptor at the surface of the B-lymphocyte in later stages of cell maturation. There is a similar T-cell gene rearrangement sequence to form the component parts of the T-cell surface receptor (TCR), although the TCR is not an Ig molecule. The sequence of gene rearrangement and Ig or T-cell receptor construction can be followed by nucleic acid probe techniques. Later-stage T-cells can also be identified by the classic erythrocyte (E) rosette technique in which sheep red blood cells (RBCs) spontaneously aggregate around the T-cell to form a “rosette.” The classic procedure for measuring T-cell function is the migration inhibition factor (MIF) assay.

The same principles and technology can be applied to the non-Hodgkin’s lymphomas. Demonstration that almost all cells of a lymphocytic proliferation have the same (clonal) Ig or TCR rearrangement stage gives strong evidence for neoplasia (lymphoma or myeloma). There are some uncommon nonmalignant clonal lymphocyte-associated conditions such as angioimmunoblastic lymphadenopathy, posttransplant lymphoid proliferation or pseudotumor, and so-called monoclonal gammmopathy of undetermined significance. However, some patients with these conditions later go on to malignancy. The type of receptor gene rearrangement differentiates B- and T-cell lineage; Ig clonal light chain rearrangement is diagnostic for B-cell tumors, and clonal TCR rearrangement without light chain rearrangement is diagnostic of T-cell tumors.