B-CHRONIC LYMPHOCYTIC LEUKEMIAS CAN UNDERGO ISOTYPE SWITCHING IN-VIVOAND CAN BE INDUCED TO DIFFERENTIATE AND SWITCH IN-VITRO

B-chronic lymphocytic leukemias (B-CLL) represent expanded clones of r esting B lymphocytes that mostly express surface IgM (slgM). The prese nt study shows that B-CLL cells, freshly isolated from two patients, w ere slgM(+), slgG(-), and slgA(-) but expressed IgG and IgA transcript s. cDNA cloning and sequencing showed that the VDJ segments associated to gamma and alpha heavy chain transcripts are identical to those fro m mu transcripts, thus showing that B lymphocytes giving rise to CLL c ells have undergone isotype switching in vivo. Stimulation of these B- CLL cells through surface CD40 in the presence of interleukin-10 induc ed them to secrete IgG and IgA, proving that they can also differentia te into Ig-secreting cells. Finally, CD40-stimulated B-CLL cells were induced to switch towards IgE in response to interleukin-l, as shown b y the presence of specific VDJ-C epsilon transcripts and the secretion of IgE. Therefore, B-CLL cells tested herein can undergo isotype swit ching in vivo and can be induced to undergo further isotype switching and differentiation in vitro. (C) 1996 by The American Society of Hema tology.