|
|
 Previous Article | Table of Contents | Next Article 
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
Surinder S. Sahota,
Richard Garand,
Regis Bataille,
Alastair J. Smith, and
Freda K. Stevenson
From the Molecular Immunology Group, Tenovus Laboratory, Southampton
University Hospitals, Southampton, UK; and the Centre Hospitalier
Universitaire de Nantes, Institut de Biologie, Nantes Cedex, France.
An unusual group of human B-cell tumors with cellular features of
chronic lymphocytic leukemia or lymphoplasmacytoid leukemia, together
with high levels of a monoclonal IgG serum protein, has been
investigated. Analysis of tumor-derived VH genes of
neoplastic B lymphocytes was used to determine the clonal relationship
between the IgM expressed or secreted by the tumor cells and the IgG
serum paraprotein. In all five cases, VH gene sequences
showed transcripts of IgM and IgG of common clonal origin. Sequences
were derived from VH3 (4 of 5) and VH1 (1 of 5)
families and were all highly somatically mutated with strong evidence
for antigen selection. There was no intraclonal variation detectable in
either IgM or IgG sequences. In 3 of 5 cases, in which monoclonal IgM
and IgG were found in serum, the VH genes combined to Cµ
or C showed identical mutational patterns. However, in 2 of 5 cases,
in which IgM was confined to cell expression with only monoclonal IgG
in serum, sequences of the VH transcripts of IgM and IgG
showed many shared mutations but also numerous differences. In these
cases, the level of mutation was similar in IgM and IgG and both
appeared to be antigen selected. In summary, the final neoplastic event in this group of tumors has apparently occurred at the point of isotype
switch from IgM to IgG, leading to dual isotype synthesis. In the group
that secreted both isotypes, the mutation pattern was identical,
indicating either synthesis by a single cell, or silencing of
mutational activity before switching. In the group that did not secrete
IgM, cells of each isotype were distinct and reflected a divergent
mutational history.
Blood, Vol. 91 No. 1 (January 1), 1998:
pp. 238-243
© 1998 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:
|
|
|
|
 
L. Lode, S. S. Sahota, S. Wuilleme, S. Richebourg, M. Eveillard, R. Bataille, H. A. Loiseau, and R. Garand
IgG-Secreting B-Cell Lymphoplasmocytoid Leukaemia : Molecular Characterization of Igh Rearrangements.
Blood (ASH Annual Meeting Abstracts),
November 16, 2008;
112(11):
1778 - 1778.
[Abstract]
|
|
|
|
|
|
|
H. Avet-Loiseau, R. Garand, L. Lode, J.-L. Harousseau, and R. Bataille
Translocation t(11;14)(q13;q32) is the hallmark of IgM, IgE, and nonsecretory multiple myeloma variants
Blood,
February 15, 2003;
101(4):
1570 - 1571.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. S. Sahota, F. Forconi, C. H. Ottensmeier, D. Provan, D. G. Oscier, T. J. Hamblin, and F. K. Stevenson
Typical Waldenstrom macroglobulinemia is derived from a B-cell arrested after cessation of somatic mutation but prior to isotype switch events
Blood,
July 30, 2002;
100(4):
1505 - 1507.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Forconi, S. S. Sahota, D. Raspadori, C. I. Mockridge, F. Lauria, and F. K. Stevenson
Tumor cells of hairy cell leukemia express multiple clonally related immunoglobulin isotypes via RNA splicing
Blood,
August 15, 2001;
98(4):
1174 - 1181.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. H. Ottensmeier and F. K. Stevenson
Isotype switch variants reveal clonally related subpopulations in diffuse large B-cell lymphoma
Blood,
October 1, 2000;
96(7):
2550 - 2556.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. S. Sahota, R. Garand, R. Mahroof, A. Smith, N. Juge-Morineau, F. K. Stevenson, and R. Bataille
VH Gene Analysis of IgM-Secreting Myeloma Indicates an Origin From a Memory Cell Undergoing Isotype Switch Events
Blood,
August 1, 1999;
94(3):
1070 - 1076.
[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]
|
|
|
|
|
