Leukemia Research Vol. 13, No. 1, pp. 31-37. 1989. 0145-2126/89 $3.00 + .00 Printed in Great Britain. Pergamon Press plc HIGHER T-CELL IMBALANCE AND GROWTH FACTOR RECEPTOR EXPRESSION IN B-CELL CHRONIC LYMPHOCYTIC LEUKEMIA (B-CLL) AS COMPARED TO MONOCLONAL B-CELL LYMPHOCYTOSIS OF UNDETERMINED SIGNIFICANCE (B-MLUS) CARLOS GARCIA,* ANDERS ROSI~N,§ EVA KIMBY,¶ MIGUEL AGUILAR-SANTELISES,[I MIKAEL JONDAL,[ I MAGNUS BJORKHILM,~ GORAN HOLM:I: and HAKAN MELLSTEDT*t * Immunological Research Laboratory, t Dept of Oncology (Radioumhemmet), $ Dept of Medicine, Karolinska Hospital, § Dept of Medical Cell Genetics, Hybridoma Group and [1Dept of Immunology, Karolinska Institute, and ¶ Dept of Medicine, Danderyd Hospital, Stockholm, Sweden (Received 10 May 1988. Rev&ion accepted 21 August 1988) Abstraet--The surface marker phenotype of lymphocytes derived from 12 patients with B-CLL was compared to that of lymphocytes from 10 patients with an other monoclonal but clinical benign form of B-cell proliferative disorder termed monoclonal B-cell lymphocytosis of undetermined significance (B-MLUS). A panel of well characterized monoclonal antibodies was used for the surface marker determinations. The mean total number of B cells (CD20) was 8.5 × 109/1 in B-MLUS as compared to 44 x 109/1 in B-CLL (p < 0.001). B-CLL had a greater imbalance in T-cell subpopulations than B- MLUS and healthy controls. Total numbers of CD3 ÷, CD8 ÷ cells as well as cells expressing the NK- related antigens (CD16, Leu-7) and IL-2 receptor (CD25) bearing lymphocytes were statistically significant higher in B-CLL than in B-MLUS. Analyses of B-cell enriched populations showed that B-CLL represented B cells of an early maturation stage, whereas B cells from B-MLUS were more mature as judged by the loss of the CD21 surface marker. A larger fraction of B cells in B-CLL compared to B-MLUS exhibited a higher activation stage as revealed by the expression of the CD21, CD25 and CD35 structures as well as the FMC7 antigen. Key words: Phenotypes, lymphoid cells, B-CLL, B-MLUS. INTRODUCTION HUMAN lymphocytic leukemias are heterogeneous in their phenotypic appearance, clinical presentations and response to therapy [1-3]. B-CLL is often con- sidered as a neoplastic accumulation of small resting B lymphocytes which have inappropriately been "frozen" at an early stage of maturation [4--6]. An understanding of the processes involved in the growth and differentiation of normal B cells is now being analysed by defined growth factors and func- tional cell surface antigens. B-CLL cells are characterized by a decreased amount of smlg. The low amount of smlg might explain why it is difficult or impossible to stimulate Abbreviations: B-CLL, B-cell chronic lymphocytic leu- kemia; B-MLUS, B-cell monoclonal lymphoeytosis of undetermined significance; srnlg, surface membrane immunoglobulin; IFL, immunofluoroscence; srnpv, sur- face membrane poly-valent Ig. Correspondence to: Dr Hhkan Mellstedt, Dept of Oncology, Radiumhemmet, Karolinska Hospital, S-104 01 Stockholm, Sweden. 31 B-CLL cells by anti-Ig and that stronger signals like TPA [7] are needed. B-CLL cells express receptors for mouse erythrocytes, carry Fc-receptors for IgG and express high amounts of C3d receptors (CD21), as well as Ia and the B-cell antigens CD19, CD20, and lower amount of C3b receptors (CD35) [2, 8]. Another antigen associated with B-CLL cells is CD5, previously thought to be restricted to T lymphocytes [9]. The TQ1 antigen, found on the inducer/sup- pressor subset within the T-helper population [1, 8] and the IL-2 receptors (CD25) are also found on B- CLL cells [10, 11]. B-CLL is frequently accompanied by various blood T-cell abnormalities including an imbalance in the major T-cell subsets [12-16], and a defect T-cell function [17-19]. The natural killer (NK) cell activity has been reported abnormal in B-CLL patients [18, 20] as has the expression of NK-cell related surface antigens [21, 221 . Some patients diagnosed as "B-CLL" have a monoclonal B-cell lymphocytosis and a lymphoid