scholarly journals Lack of Allelic Exclusion in B Cell Chronic Lymphocytic Leukemia

1997 ◽  
Vol 185 (8) ◽  
pp. 1435-1446 ◽  
Author(s):  
Laura Z. Rassenti ◽  
Thomas J. Kipps
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Heavy Chain ◽  
Protein A ◽  
Lymphocytic Leukemia ◽  
Allelic Exclusion ◽  
Staphylococcal Protein A ◽  
Vh Genes ◽  
Ig Heavy Chain ◽  
Cell Chronic Lymphocytic Leukemia

We determined the immunoglobulin (Ig) VH subgroup expressed by the leukemia cells of 108 patients with B cell chronic lymphocytic leukemia (CLL). Surprisingly, we found that six samples (5%) each expressed Ig of more than one VH subgroup. Southern blot analysis demonstrated that these samples each had rearrangements involving both Ig heavy chain alleles. Nucleic acid sequence analyses of the Ig cDNA revealed each to express two functional Ig VH genes: VH3-33 and VH4-39; VH3-7 and VH4-39; VH3-23 and VH4-61; VH2-70 and VH3-30.3; or VH3-30 and VH4-b (DP67). One sample expressed three Ig VH genes: VH2-70, VH3-7, and VH4-59. Despite having more than one Ig heavy chain transcript, each sample was found to express only one functional Ig light chain. From the primary sequence, we deduced that the Ig of some of these CLL samples should react with Lc1, a monoclonal antibody (mAb) reactive with a supratypic cross-reactive idiotype present on Ig encoded by a subgroup of Ig VH4 genes (namely, VH4-39, VH4-b [DP-67], VH4-59, or VH4-61), and B6, an mAb that reacts with Ig encoded by certain Ig VH3 genes (namely, VH3-23, VH3-30, or VH3-30.3), and/or modified staphylococcal protein A (SpA), a 45-kilodalton bacterial “superantigen” that reacts with most Ig of the VH3 subgroup. Flow cytometric analyses revealed that such samples did in fact react with Lc1 and B6 and/or SpA, but not with control mAbs of irrelevant specificity. This study demonstrates that a subset of CLL patients have leukemic B cells that express more than one functional Ig heavy chain.

scholarly journals Lack of allelic exclusion and isotype switching in B cell chronic lymphocytic leukemia

2001 ◽  
Vol 68 (4) ◽  
pp. 295-297 ◽  
Author(s):  
Yuta Katayama ◽  
Akira Sakai ◽  
Shinya Katsutani ◽  
Yasuo Takimoto ◽  
Akiro Kimura
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Lymphocytic Leukemia ◽  
Allelic Exclusion ◽  
Isotype Switching ◽  
Cell Chronic Lymphocytic Leukemia

Serum BAFF (B-Cell Activating Factor of the TNF Family) Compared with Immunoglobulin Heavy-Chain Mutation Status, ZAP-70 and CD38 as a Predictor of Time to First Treatment in Early B-Cell Chronic Lymphocytic Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3093-3093
Author(s):  
Stefano Molica ◽  
Gaetano Vitelli ◽  
Giovanna Cutrona ◽  
Giovanna Digiesi ◽  
Rosanna Mirabelli ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Heavy Chain ◽  
Immunoglobulin Heavy Chain ◽  
Serum Levels ◽  
Lymphocytic Leukemia ◽  
B Cell Activating Factor ◽  
Mutational Status ◽  
Time To First Treatment ◽  
Cell Chronic Lymphocytic Leukemia

Abstract We analyzed the correlation between well-established biological parameters of prognostic relevance in B-cell chronic lymphocytic leukemia [CLL] (i.e, mutational status of the immunoglobulin heavy chain variable region [IgVH], ZAP-70- and CD38-expression) and serum levels of BAFF (B-cell activating factor of the TNF family) by evaluating the impact of these variables on the time to first treatment [TFT] in a series of 69 previously untreated Binet stage A B-cell CLL patients. By using a commercial ELISA (R & D Systems, USA) we found that higher levels of BAFF characterized more frequently patients with Rai stage 0 (P=0.008) and mutated IgVH (P=0.03). In contrast, peripheral blood lymphocytosis (P=0.06), serum β2-m (P=0.159), LDH (P=0.333) and percentage of ZAP-70-positive (P=0.242) or CD38-positive B-CLL cells (P=0.142) did not reflect circulating levels of BAFF. The relationship among various bio-pathological parameters, analyzed by the multiple correspondence analysis (MCA), showed two different clinico-biological profiles. The first, characterized by higher BAFF serum levels (i.e., > 336 ng/mL), presence of mutation in the IgVH, low percentage of CD38-positive B-CLL cells (< 30%) and low LDH was associated with a stable pattern of disease generally not requiring therapy. The second, defined by lower BAFF levels, absence of mutation in the IgVH, high percentage of CD38- positive B-CLL cells and high LDH was associated with a more progressive pattern of disease and a shorter TFT. After a median follow-up time of 35 months (range, 2–120 months) 26 (37.6%) out of 69 patients experienced a need for chemotherapy. Kaplan-Meier estimates of patientsTFT, plotted after searching the best cut-off for BAFF (i.e., 336 ng/mL), demonstrated that low BAFF concentration was associated with a shorter TFT (median TFT 36 months) while median was not reached by patients with BAFF levels higher than 336 ng/mL (P<0.0001). Along with lower serum levels of BAFF (Hazard Ratio [HR], 0.19; P<0.0001), the univariate Cox proportional hazard model identified absence of mutation in IgVH (HR, 0.17; P<0.0001), CD38-positivity (HR, 3.32; P=0.01) and lower platelet count (HR, 0.19; P=0.03) as predictor of shorter TFT. Finally, in multivariate analysis only mutational status of IgVH (HR, 0.25; P=0.007) and serum concentration of BAFF (HR, 034; P=0.04) affected significantly TFT. Our results indicate that in early B-cell CLL clinico-biological profile including among other parameters BAFF may provide a useful insight into the complex interrelationship of prognostic variables and semplify their interpretation. The possible presence of BAFF isoform in B-CLL could peraphs account for the unexpected correlation between low soluble BAFF levels and poor clinical outcome in patients with early disease.

Molecular Analysis of Rearranged VH Genes during B Cell Chronic Lymphocytic Leukemia: Intraclonal Stability is Frequent but not Constant

1994 ◽  
Vol 14 (1-2) ◽  
pp. 55-69 ◽  
Author(s):  
Anne-Sophie Korganow ◽  
Thierry Martin ◽  
Jean-Christophe Weber ◽  
Bruno Lioure ◽  
Patrick Lutz ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Molecular Analysis ◽  
Lymphocytic Leukemia ◽  
Vh Genes ◽  
Cell Chronic Lymphocytic Leukemia

Most immunoglobulin heavy chain switch mu rearrangements in B-cell chronic lymphocytic leukemia are internal deletions

FEBS Letters ◽  
2002 ◽  
Vol 518 (1-3) ◽  
pp. 119-123 ◽  
Author(s):  
Elena Nardini ◽  
Simona Rizzi ◽  
Daniela Capello ◽  
Umberto Vitolo ◽  
Gianluca Gaidano ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Heavy Chain ◽  
Immunoglobulin Heavy Chain ◽  
Lymphocytic Leukemia ◽  
Cell Chronic Lymphocytic Leukemia

scholarly journals A mutated B cell chronic lymphocytic leukemia subset that recognizes and responds to fungi

2013 ◽  
Vol 210 (1) ◽  
pp. 59-70 ◽  
Author(s):  
Robbert Hoogeboom ◽  
Kok P.M. van Kessel ◽  
Frans Hochstenbach ◽  
Thera A. Wormhoudt ◽  
Roy J.A. Reinten ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Lymphocytic Leukemia ◽  
Antigenic Specificity ◽  
B Cell Receptors ◽  
Light Chains ◽  
Cognate Antigen ◽  
Ig Heavy Chain ◽  
Cell Chronic Lymphocytic Leukemia ◽  
Human B Cell

B cell chronic lymphocytic leukemia (CLL), the most common leukemia in adults, is a clonal expansion of CD5+CD19+ B lymphocytes. Two types of CLLs are being distinguished as carrying either unmutated or somatically mutated immunoglobulins (Igs), which are associated with unfavorable and favorable prognoses, respectively. More than 30% of CLLs can be grouped based on their expression of stereotypic B cell receptors (BCRs), strongly suggesting that distinctive antigens are involved in the development of CLL. Unmutated CLLs, carrying Ig heavy chain variable (IGHV) genes in germline configuration, express low-affinity, poly-, and self-reactive BCRs. However, the antigenic specificity of CLLs with mutated IGHV-genes (M-CLL) remained elusive. In this study, we describe a new subset of M-CLL, expressing stereotypic BCRs highly specific for β-(1,6)-glucan, a major antigenic determinant of yeasts and filamentous fungi. β-(1,6)-glucan binding depended on both the stereotypic Ig heavy and light chains, as well as on a distinct amino acid in the IGHV-CDR3. Reversion of IGHV mutations to germline configuration reduced the affinity for β-(1,6)-glucan, indicating that these BCRs are indeed affinity-selected for their cognate antigen. Moreover, CLL cells expressing these stereotypic receptors proliferate in response to β-(1,6)-glucan. This study establishes a class of common pathogens as functional ligands for a subset of somatically mutated human B cell lymphomas.

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