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 ◽  
...  

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.

1994 ◽  
Vol 56 (3) ◽  
pp. 439-445 ◽  
Author(s):  
Zhenping Zhu ◽  
Tarunendu Ghose ◽  
David Hoskin ◽  
Christine L. Y. Lee ◽  
Louis A. Fernandez ◽  
...  

1992 ◽  
Vol 176 (4) ◽  
pp. 1073-1081 ◽  
Author(s):  
J Cai ◽  
C Humphries ◽  
A Richardson ◽  
P W Tucker

B cell chronic lymphocytic leukemia (CLL) is the malignant, monoclonal equivalent of a human CD5+ B cell. Previous studies have shown that the VH and VL genes rearranged and/or expressed in CLL have few and apparently random mutations. However, in this study, we have found that the rearranged VH251 gene, one of the three-membered VH5 family, has extensive and selective mutations in B-CLL cells. Somatic mutation at the nucleotide level is 6.03% in B-CLLs whereas the somatic mutation levels are much lower in CD5+ and CD5- cord B cells, adult peripheral blood B cells, and Epstein-Barr virus-transformed CD5+ B cell lines (0.45, 0.93, and 1.92%, respectively). Complementary determining region 1 (CDR1) mutation in CLLs is particularly prevalent, and interchanges in CDRs often lead to acquisition of charge. Analysis of somatic mutations and mutations to charged residues demonstrated that the mutations in CLLs are highly selected.


2001 ◽  
Vol 25 (6) ◽  
pp. 435-440 ◽  
Author(s):  
Jamie K Waselenko ◽  
Michael R Grever ◽  
Charlotte A Shinn ◽  
Ian W Flinn ◽  
John C Byrd

1997 ◽  
Vol 185 (8) ◽  
pp. 1435-1446 ◽  
Author(s):  
Laura Z. Rassenti ◽  
Thomas J. Kipps

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.


1988 ◽  
Vol 28 (3) ◽  
pp. 146-154 ◽  
Author(s):  
T. Ghose ◽  
C. L. Y. Lee ◽  
G. Faulkner ◽  
L. A. Fernandez ◽  
S. H. S. Lee

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