Immunoglobulin gene rearrangement and cell surface antigen expression in acute lymphocytic leukemias of T cell and B cell precursor origins

• Published in: The Journal of clinical investigation 1983-02, Vol.71 (2), p.301-313
• Main Authors: Korsmeyer, S J, Arnold, A, Bakhshi, A, Ravetch, J V, Siebenlist, U, Hieter, P A, Sharrow, S O, LeBien, T W, Kersey, J H, Poplack, D G, Leder, P, Waldmann, T A
• Format: Article
• Language: English
• Subjects: B-Lymphocytes - immunology; Genes; Genetic Code; Humans; Immunoglobulin Heavy Chains - genetics; Phenotype; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - immunology; Receptors, Antigen, B-Cell - genetics; Receptors, Antigen, T-Cell - genetics; Recombination, Genetic; T-Lymphocytes - immunology
• ISSN: 0021-9738
• DOI: 10.1172/JCI110770

We have explored the relationship among immunoglobulin gene rearrangement, cytoplasmic immunoglobulin production, and cell surface antigen expression within 37 cases of acute lymphocytic leukemia. All 12 cases of the T cell type had germ-line kappa and lambda genes and 11 of 12 had germ-line heavy chain genes. In contrast, all 25 cases of the "non-T, non-B" classification, which lacked both definitive T cell markers and surface immunoglobulin, had rearranged immunoglobulin genes, indicating that they represent precursor cells already committed to the B cell lineage at the gene level. 14 had rearranged heavy chain genes, yet retained germ-line light chain genes, whereas 11 cases had both heavy and light chain gene reorganizations. All patterns of immunoglobulin gene rearrangement predicted by a model that proceeds from heavy chain gene recombination to light chain genes were observed. Despite the uniform presence of rearranged immunoglobulin genes, only five cases produced cytoplasmic mu-chain, one exceptional case produced gamma-chain, and another produced only lambda-chain. The cases of B cell precursor type that do not produce immunoglobulin may represent cells that frequently possess ineffectively rearranged immunoglobulin genes. Included in this group may be a set of cells trapped within the B cell precursor series because their ineffective rearrangements have eliminated certain gene subsegments necessary for the assemblage of an effective heavy chain gene. All seven cases of the non-T, non-B subgroup that bore HLA-DR but lacked CALLA (the common acute lymphocytic leukemia-associated antigen) represented the earliest recognizable stage of B cell precursors with rearranged heavy chain genes but germ-line light chain genes. Correlations here suggest that cells entering B cell development express HLA-DR and rearrange heavy chain genes before the expression of a B cell-associated antigen recognized by the antibody BA-1, the antigen CALLA, and any subsequent light chain gene rearrangements.