B-chronic lymphocytic leukemias can undergo isotype switching in vivo and can be induced to differentiate and switch in vitro.
نویسندگان
چکیده
B-chronic lymphocytic leukemias (B-CLL) represent expanded clones of resting B lymphocytes that mostly express surface IgM (sIgM). The present study shows that B-CLL cells, freshly isolated from two patients, were sIgM+, sIgG-, and sIgA- but expressed IgG and IgA transcripts. cDNA cloning and sequencing showed that the VDJ segments associated to gamma and alpha heavy chain transcripts are identical to those from mu transcripts, thus showing that B lymphocytes giving rise to CLL cells have undergone isotype switching in vivo. Stimulation of these B-CLL cells through surface CD40 in the presence of interleukin-10 induced them to secrete IgG and IgA, proving that they can also differentiate into Ig-secreting cells. Finally, CD40-stimulated B-CLL cells were induced to switch towards IgE in response to interleukin-4, as shown by the presence of specific VDJ-C epsilon transcripts and the secretion of IgE. Therefore, B-CLL cells tested herein can undergo isotype switching in vivo and can be induced to undergo further isotype switching and differentiation in vitro.
منابع مشابه
IgM-producing chronic lymphocytic leukemia cells undergo immunoglobulin isotype-switching without acquiring somatic mutations.
The malignant B cells in chronic lymphocytic leukemia (CLL) typically express low-density membrane IgM or IgM/IgD. In vitro experiments have shown that the CLL cells can be induced to differentiate into cells that secrete immunoglobulin (Ig) and can occasionally undergo heavy (H) chain class switching. We now show that the CLL cells also undergo isotype-switching in vivo, since gamma and/or alp...
متن کاملFurther evidence for in vivo isotype switching in B-cell chronic lymphocytic leukemia.
In a recent article in Blood, Malison et a l l have reported experimental evidence in support of in vivo isotype switching in B-cell chronic lymphocytic leukemia (CLL). The evidence was that freshly isolated sIgM’ sIgGsIgK B-CLL cells nevertheless express IgG and IgA transcripts that have identical VDJ segments and that these cells may be induced in vivo to secrete IgG and IgA. Based on our own...
متن کاملInhibition of IL-13 by Antisense Oligonucleotide Changes Immunoglobulin Isotype Profile in Cultured B-Lymphocytes
The link between IL-13 and bronchial hyper-responsiveness has brought this cytokine as a potential therapeutic target for asthma and allergic diseases. At the present study, we address the role of B cell derived IL-13 in the IgE and other immunoglobulin development. Antisense oligo for human IL-13 m-RNA was used to study IgE down regulation. Human B-lymphocytes were purified by positive selecti...
متن کاملChronic lymphocytic leukemia B cells expressing AID display dissociation between class switch recombination and somatic hypermutation.
In B cells, somatic hypermutation (SHM) and class switch recombination (CSR) depend on the activation-induced cytidine deaminase (AID) gene product, although the precise mode of action of AID remains unknown. Because some chronic lymphocytic leukemia (CLL) B cells can undergo CSR without SHM, it constitutes a useful model to dissect AID function. In this work, we have studied AID expression, th...
متن کاملDetection of aberrant isotype switch recombination in low-grade and high-grade gastric MALT lymphomas.
Gastric mucosa-associated lymphoid tissue (MALT) lymphoma originates from reactive lymphocytic infiltrates during chronic gastritis, closely associated with Helicobacter pylori infection. MALT lymphomas may be either "low grade" or "high grade," and transformation from low grade to high grade can occur. To obtain information on the maturational state of MALT lymphoma cells, we investigated thei...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Blood
دوره 87 2 شماره
صفحات -
تاریخ انتشار 1996