|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 93 No. 7 (April 1), 1999:
pp. 2327-2335
An Alternatively Spliced Form of CD79b Gene May Account for Altered
B-Cell Receptor Expression in B-Chronic Lymphocytic Leukemia
A. Alfarano,
S. Indraccolo,
P. Circosta,
S. Minuzzo,
A. Vallario,
R. Zamarchi,
A. Fregonese,
F. Calderazzo,
A. Faldella,
M. Aragno,
C. Camaschella,
A. Amadori, and
F. Caligaris-Cappio
From Dipartimento di Scienze Biomediche e Oncologia Umana,
Università di Torino; Divisione Universitaria di Immunologia
Clinica e Allergologia, Ospedale Mauriziano Umberto I°, Torino;
Laboratorio di Immunologia Oncologica, IRCC, Candiolo;
IST-Biotechnology Section, Padua; Dipartimento di Scienze Oncologiche e
Chirurgiche, Sezione di Oncologia, Università di Padova, Padova;
and Dipartimento di Scienze Cliniche e Biologiche, Università di
Torino, Torino, Italy.
Several functional anomalies of B-chronic lymphocytic leukemia
(B-CLL) cells may be explained by abnormalities of the B-cell receptor
(BCR), a multimeric complex formed by the sIg homodimer and the
noncovalently bound heterodimer Ig /Ig (CD79a/CD79b). Because the
expression of the extracellular Ig-like domain of CD79b has been
reported to be absent in the cells of most CLL cases, we have
investigated the molecular mechanisms that may account for this defect.
Peripheral blood lymphocytes (PBL) from 50 patients and two cell lines
(MEC1, MEC2) obtained from the PBL of one of them were studied. MEC1,
MEC2, and 75% of CLL cases did not express detectable levels of the
extracellular Ig-like domain of CD79b, which was nevertheless present
in greater than 80% CD19+ cells from normal donors. In
healthy subjects the expression of CD79b was equally distributed in
CD5+ and CD5 B-cell subsets. Reverse
transcription-polymerase chain reaction (RT-PCR) analysis of CD79b RNA
from all patients and from MEC1 and MEC2 cell lines consistently
yielded two fragments of different size (709 bp and 397 bp). The 709-bp
band corresponds to CD79b entire transcript; the 397-bp band
corresponds to an alternatively spliced form lacking exon 3 that
encodes the extracellular Ig-like domain. Both fragments were also
visible in normal PBL. The expression of the 397-bp fragment was
increased in normal activated B cells, while no difference was seen
between CD5+ and CD5 B cells. To obtain a
more accurate estimate of the relative proportions of the two spliced
forms, a radioactive PCR was performed in 13 normal and 22 B-CLL
samples and the results analyzed using a digital imager. The mean value
of the CD79b to the CD79b internally deleted ratio was 0.64 ± 0.20 SD
in normal donors and 0.44 ± 0.27 SD in B-CLL (P = .01).
Direct sequencing of 397-bp RT-PCR products and of genomic DNA
corresponding to exon 3 from MEC1, MEC2, their parental cells, and five
fresh B-CLL samples did not show any causal mutation. Single-strand
conformation polymorphism analysis of exon 3 performed in 18 additional
B-CLL cases showed a single abnormal shift corresponding to a
TGT  TGC polymorphic change at amino acid 122. We propose a role
for the alternative splicing of CD79b gene in causing the reduced
expression of BCR on the surface of B-CLL cells. As normal B cells also
present this variant, the mechanism of CD79b posttranscriptional
regulation might reflect the activation stage of the normal B cell from
which B-CLL derives.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
L. Chen, L. Huynh, J. Apgar, L. Tang, L. Rassenti, A. Weiss, and T. J. Kipps
ZAP-70 enhances IgM signaling independent of its kinase activity in chronic lymphocytic leukemia
Blood,
March 1, 2008;
111(5):
2685 - 2692.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. H. Khan, S. Mendoza, P. Rhyne, M. Ziman, J. Tuscano, D. Eisinger, H.-J. Kung, and P. A. Luciw
Multiplex Analysis of Intracellular Signaling Pathways in Lymphoid Cells by Microbead Suspension Arrays
Mol. Cell. Proteomics,
April 1, 2006;
5(4):
758 - 768.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Vuillier, G. Dumas, C. Magnac, M.-C. Prevost, A. I. Lalanne, P. Oppezzo, E. Melanitou, G. Dighiero, and B. Payelle-Brogard
Lower levels of surface B-cell-receptor expression in chronic lymphocytic leukemia are associated with glycosylation and folding defects of the {micro} and CD79a chains
Blood,
April 1, 2005;
105(7):
2933 - 2940.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Nedellec, Y. Renaudineau, A. Bordron, C. Berthou, N. Porakishvili, P. M. Lydyard, J.-O. Pers, and P. Youinou
B Cell Response to Surface IgM Cross-Linking Identifies Different Prognostic Groups of B-Chronic Lymphocytic Leukemia Patients
J. Immunol.,
March 15, 2005;
174(6):
3749 - 3756.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Chiorazzi, K. R. Rai, and M. Ferrarini
Chronic Lymphocytic Leukemia
N. Engl. J. Med.,
February 24, 2005;
352(8):
804 - 815.
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. K. Stevenson and F. Caligaris-Cappio
Chronic lymphocytic leukemia: revelations from the B-cell receptor
Blood,
June 15, 2004;
103(12):
4389 - 4395.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Lanham, T. Hamblin, D. Oscier, R. Ibbotson, F. Stevenson, and G. Packham
Differential signaling via surface IgM is associated with VH gene mutational status and CD38 expression in chronic lymphocytic leukemia
Blood,
February 1, 2003;
101(3):
1087 - 1093.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. S. Cragg, H. T. C. Chan, M. D. Fox, A. Tutt, A. Smith, D. G. Oscier, T. J. Hamblin, and M. J. Glennie
The alternative transcript of CD79b is overexpressed in B-CLL and inhibits signaling for apoptosis
Blood,
October 16, 2002;
100(9):
3068 - 3076.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Gurrieri, P. McGuire, H. Zan, X.-J. Yan, A. Cerutti, E. Albesiano, S. L. Allen, V. Vinciguerra, K. R. Rai, M. Ferrarini, et al.
Chronic Lymphocytic Leukemia B Cells Can Undergo Somatic Hypermutation and Intraclonal Immunoglobulin VHDJH Gene Diversification
J. Exp. Med.,
September 2, 2002;
196(5):
629 - 639.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. N. Damle, F. Ghiotto, A. Valetto, E. Albesiano, F. Fais, X.-J. Yan, C. P. Sison, S. L. Allen, J. Kolitz, P. Schulman, et al.
B-cell chronic lymphocytic leukemia cells express a surface membrane phenotype of activated, antigen-experienced B lymphocytes
Blood,
May 13, 2002;
99(11):
4087 - 4093.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E Matutes
New additions to antibody panels in the characterisation of chronic lymphoproliferative disorders
J. Clin. Pathol.,
March 1, 2002;
55(3):
180 - 183.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Bernal, R. D. Pastore, Z. Asgary, S. A. Keller, E. Cesarman, H.-C. Liou, and E. J. Schattner
Survival of leukemic B cells promoted by engagement of the antigen receptor
Blood,
November 15, 2001;
98(10):
3050 - 3057.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. S. Malone, M. D. Miner, J. R. Doerr, J. P. Jackson, S. E. Jacobsen, R. Wall, and M. Teitell
CmC(A/T)GG DNA methylation in mature B cell lymphoma gene silencing
PNAS,
August 10, 2001;
(2001)
181206898.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Z. Rassenti and T. J. Kipps
Expression of Ig-beta (CD79b) by chronic lymphocytic leukemia B cells that lack immunoglobulin heavy-chain allelic exclusion
Blood,
April 15, 2000;
95(8):
2725 - 2727.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Nilsson, O. Soderberg, K. Nilsson, and A. Rosen
Thioredoxin prolongs survival of B-type chronic lymphocytic leukemia cells
Blood,
February 15, 2000;
95(4):
1420 - 1426.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. S. Gordon, R. M. Kato, F. Lansigan, A. A. Thompson, R. Wall, and D. J. Rawlings
Aberrant B cell receptor signaling from B29 (Igbeta , CD79b) gene mutations of chronic lymphocytic leukemia B cells
PNAS,
May 9, 2000;
97(10):
5504 - 5509.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. S. Malone, M. D. Miner, J. R. Doerr, J. P. Jackson, S. E. Jacobsen, R. Wall, and M. Teitell
CmC(A/T)GG DNA methylation in mature B cell lymphoma gene silencing
PNAS,
August 28, 2001;
98(18):
10404 - 10409.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
