Function and X Chromosome Inactivation Analysis of B Lymphocytes in Myelodysplastic Syndromes with Immunological Abnormalities

To investigate the pathogenesis of immunological abnormalities (IA) in myelodysplastic syndrome (MDS), we examined B cells for their ability to produce cytokine and their X chromosome inactivation pattern (XCIP). An IA was defined as being positive for at least one autoimmune laboratory test (e.g. antinuclear antibody, rheumatoid factor). Seventy-three MDS patients [65 with refractory anemia (RA), 3 with RA with excess blasts (RAEB), and 5 with RAEB in transformation] were examined; 47 had IA and 26 had no IA. To examine the function of B cells in MDS, the production of interleukin (IL)-6 and IL-10 was measured in cultures of purified B cells with or without stimulators. Both IL-6 and IL-10 production rates in patients with IA were significantly higher than in patients without IA and normal controls. The skewing of XCIP of B cells was analyzed by using the polymerase chain reaction, and the skewing rate of B cell XCIP was quantitatively assayed by compared to control T lymphocytes. The skewing rate of B cells was higher in patients with IA than in those without IA and normal controls. Therefore, a small population of B cells in patients with IA might be derived from MDS clones, and be associated with the induction of IA.