|
|
 Previous Article | Table of Contents | Next Article 
Molecular characterization of IgA- and/or IgG-switched chronic lymphocytic
leukemia B cells
A Matolcsy, P Casali, RG Nador, YF Liu and DM Knowles
Department of Pathology, University Medical School of Pecs, Hungary.
The immunoglobulin (Ig) variable region (V) genes expressed by IgM chronic
lymphocytic leukemia (CLL) B cells display little or no somatic mutations.
However, preliminary findings have shown that Ig V genes of IgA and IgG
CLLs may be somatically mutated, suggesting that isotype- switched CLLs may
represent a "subtype" of the disease. To investigate the degree and nature
of somatic mutations and the role of antigen (Ag) in the clonal selection
and expansion of isotype-switched CLLs, and to determine whether specific
oncogene or tumor suppressor gene mutations are associated with
isotype-switched CLLs, we analyzed the expressed Ig VH gene, bcl-1 and
bcl-2 proto-oncogene, and p53 tumor suppressor gene configurations of 3
IgA-, 1 IgG-, and 1 IgA/ IgG-expressing CLLs. These isotype-switched CLL B
cells expressed surface HLA-DR, CD19, CD23, and CD5, and displayed no
alterations of the bcl-1 and bcl-2 oncogenes and the p53 tumor-suppressor
gene. The cDNA VH-D-JH gene sequence was joined with that of the C alpha
gene in the B cells of the three IgA CLLs, and with that of the C gamma
gene in the IgG CLL B cells. In the IgA/IgG-coexpressing CLL B cells,
identical VH-D-JH cDNA sequences were spliced to either C alpha or C gamma
genes. In all five CLLs, the pattern of C mu DNA probe hybridization to the
digested genomic DNAs was consistent with deletion of the C mu exon from
the rearranged Ig gene locus, suggesting that these CLL B cells had
undergone DNA switch recombination. In one IgA CLL, the expressed VH gene
was unmutated. In all other class-switched CLLs, the Ig VH segment gene was
mutated, but the point mutations were not associated with intraclonal
diversification. In one IgA and in the IgA/IgG-coexpressing CLL, the nature
and distribution of the mutations were consistent with Ag selection. These
findings suggest that IgA- and/or IgG-expressing CLLs represent, in their
VH gene structure, transformants of B cells at different stages of
ontogeny. They also suggest that Ag may play a role in the clonal selection
of some of these isotype-switched leukemic cells, but bcl-1 and bcl-2
oncogene rearrangements and p53 tumor suppressor gene mutation are not
associated with the pathogenesis of isotype-switched CLLs.
Volume 89,
Issue 5,
pp. 1732-1739,
03/01/1997
Copyright © 1997 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
K. N. Potter, C. I. Mockridge, L. Neville, I. Wheatley, M. Schenk, J. Orchard, A. S. Duncombe, G. Packham, and F. K. Stevenson
Structural and Functional Features of the B-Cell Receptor in IgG-Positive Chronic Lymphocytic Leukemia.
Clin. Cancer Res.,
March 15, 2006;
12(6):
1672 - 1679.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Noy, R. Verma, M. Glenn, P. Maslak, Z. U. Rahman, J. R. Keenan, M. Weiss, D. Filippa, and A. D. Zelenetz
Clonotypic polymerase chain reaction confirms minimal residual disease in CLL nodular PR: results from a sequential treatment CLL protocol
Blood,
April 1, 2001;
97(7):
1929 - 1936.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Nardini, A. Aiello, R. Giardini, M. I. Colnaghi, S. Menard, and A. Balsari
Detection of aberrant isotype switch recombination in low-grade and high-grade gastric MALT lymphomas
Blood,
February 1, 2000;
95(3):
1032 - 1038.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Matolcsy, R. G. Nador, E. Cesarman, and D. M. Knowles
Immunoglobulin VH Gene Mutational Analysis Suggests that Primary Effusion Lymphomas Derive from Different Stages of B Cell Maturation
Am. J. Pathol.,
November 1, 1998;
153(5):
1609 - 1614.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. H. Ottensmeier, A. R. Thompsett, D. Zhu, B. S. Wilkins, J. W. Sweetenham, and F. K. Stevenson
Analysis of VH Genes in Follicular and Diffuse Lymphoma Shows Ongoing Somatic Mutation and Multiple Isotype Transcripts in Early Disease With Changes During Disease Progression
Blood,
June 1, 1998;
91(11):
4292 - 4299.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. S. Sahota, R. Garand, R. Bataille, A. J. Smith, and F. K. Stevenson
VH Gene Analysis of Clonally Related IgM and IgG From Human Lymphoplasmacytoid B-Cell Tumors With Chronic Lymphocytic Leukemia Features and High Serum Monoclonal IgG
Blood,
January 1, 1998;
91(1):
238 - 243.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
