Defective expression of DR antigens in chronic lymphocytic leukemia

HLA-DR (or Ia-like) antigens which were detergent-solubilized from plasma membranes of leukemic cells of patients with chronic lymphocytic leukemia of the B cell variety were purified by gel filtration, followed by affinity chromatography on Con A-Sepharose. After radioiodination, the DR antigens were immunoprecipitated with specific antisera and analyzed by two-dimensional gel electrophoresis. Repeated mapping revealed several different patterns of DR antigen expression. Most patients (18 out of 42) gave map patterns resembling those obtained from normal peripheral blood B cells. Such maps revealed light (27 kDa) and heavy (33 kDa) DR chains as well as a non-dissociated 60 kDa DR complex. All components, and especially DR light chains, were polymorphic and could be resolved further into several characteristic isoelectric variants. Maps from eleven patients showed decreased levels of 33 and 60 kDa antigen components, while eleven further patients expressed only DR light chains. Two patients lacked detectable DR antigens. Sequential mapping of individual patients indicated that expression of 33 and 60 kDa DR components fluctuates over months. This temporal fluctuation was independent of other B cell markers, including a newly defined group of surface membrane proteins of 28 000 daltons. The patterns are reminiscent of the biochemical dedifferentiation characteristic of immunoglobulin biosynthesis seen in the plasma cell dyscrasias.