Abstract
B-cell chronic lymphocytic leukaemia (B-CLL) cells display low amounts of surface immunoglobulins (sIg). To investigate the mechanisms underlying this phenomenon, we performed a thorough study of surface and intracellular expression of the B-cell receptor (BCR) components in B-CLL cells using flow cytometry. There was an heterogeneous pattern of expression. Overall, 20 of 22 samples showed reduced sIgM levels, compared with normal B cells. Among them, three (15%) had very low to undetectable intracellular IgM levels and variable amounts of CD79a and CD79b; nine (45%) had low intracellular CD79b levels but appreciable levels of IgM and CD79a; and eight (40%) had relatively normal intracellular levels of all BCR components. To investigate whether surface BCR levels could be controlled by the rate of CD79b synthesis, adenoviral vectors encoding CD79b were generated and used for gene transfer experiments. Delivery of CD79b to non-B cells transfected with IgM and CD79a lead to high-level expression of a functional BCR. Moreover, CD79b gene transfer in a B cell line derived from a B-CLL patient and characterised by low intracellular levels of endogenous CD79b consistently increased sIgM levels. These findings indicate that the phenotype of B-CLL cells in a subset of patients may depend primarily on poor CD79b expression, and suggest that upregulation of CD79b expression may correct the phenotype of these cells.
| Original language | English |
|---|---|
| Pages (from-to) | 878-889 |
| Number of pages | 12 |
| Journal | British Journal of Haematology |
| Volume | 130 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Sep 2005 |
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Keywords
- Adenoviral vector
- B-cell receptor
- CD79b
- Chronic lymphocytic leukaemia
- Gene transfer
ASJC Scopus subject areas
- Hematology
Cite this
Heterogeneous intracellular expression of B-cell receptor components in B-cell chronic lymphocytic leukaemia (B-CLL) cells and effects of CD79b gene transfer on surface immunoglobulin levels in a B-CLL-derived cell line. / Minuzzo, Sonia; Indraccolo, Stefano; Tosello, Valeria; Piovan, Erich; Cabrelle, Anna; Trentin, Livio; Semenzato, Giampietro; Amadori, Alberto.
In: British Journal of Haematology, Vol. 130, No. 6, 09.2005, p. 878-889.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Heterogeneous intracellular expression of B-cell receptor components in B-cell chronic lymphocytic leukaemia (B-CLL) cells and effects of CD79b gene transfer on surface immunoglobulin levels in a B-CLL-derived cell line
AU - Minuzzo, Sonia
AU - Indraccolo, Stefano
AU - Tosello, Valeria
AU - Piovan, Erich
AU - Cabrelle, Anna
AU - Trentin, Livio
AU - Semenzato, Giampietro
AU - Amadori, Alberto
PY - 2005/9
Y1 - 2005/9
N2 - B-cell chronic lymphocytic leukaemia (B-CLL) cells display low amounts of surface immunoglobulins (sIg). To investigate the mechanisms underlying this phenomenon, we performed a thorough study of surface and intracellular expression of the B-cell receptor (BCR) components in B-CLL cells using flow cytometry. There was an heterogeneous pattern of expression. Overall, 20 of 22 samples showed reduced sIgM levels, compared with normal B cells. Among them, three (15%) had very low to undetectable intracellular IgM levels and variable amounts of CD79a and CD79b; nine (45%) had low intracellular CD79b levels but appreciable levels of IgM and CD79a; and eight (40%) had relatively normal intracellular levels of all BCR components. To investigate whether surface BCR levels could be controlled by the rate of CD79b synthesis, adenoviral vectors encoding CD79b were generated and used for gene transfer experiments. Delivery of CD79b to non-B cells transfected with IgM and CD79a lead to high-level expression of a functional BCR. Moreover, CD79b gene transfer in a B cell line derived from a B-CLL patient and characterised by low intracellular levels of endogenous CD79b consistently increased sIgM levels. These findings indicate that the phenotype of B-CLL cells in a subset of patients may depend primarily on poor CD79b expression, and suggest that upregulation of CD79b expression may correct the phenotype of these cells.
AB - B-cell chronic lymphocytic leukaemia (B-CLL) cells display low amounts of surface immunoglobulins (sIg). To investigate the mechanisms underlying this phenomenon, we performed a thorough study of surface and intracellular expression of the B-cell receptor (BCR) components in B-CLL cells using flow cytometry. There was an heterogeneous pattern of expression. Overall, 20 of 22 samples showed reduced sIgM levels, compared with normal B cells. Among them, three (15%) had very low to undetectable intracellular IgM levels and variable amounts of CD79a and CD79b; nine (45%) had low intracellular CD79b levels but appreciable levels of IgM and CD79a; and eight (40%) had relatively normal intracellular levels of all BCR components. To investigate whether surface BCR levels could be controlled by the rate of CD79b synthesis, adenoviral vectors encoding CD79b were generated and used for gene transfer experiments. Delivery of CD79b to non-B cells transfected with IgM and CD79a lead to high-level expression of a functional BCR. Moreover, CD79b gene transfer in a B cell line derived from a B-CLL patient and characterised by low intracellular levels of endogenous CD79b consistently increased sIgM levels. These findings indicate that the phenotype of B-CLL cells in a subset of patients may depend primarily on poor CD79b expression, and suggest that upregulation of CD79b expression may correct the phenotype of these cells.
KW - Adenoviral vector
KW - B-cell receptor
KW - CD79b
KW - Chronic lymphocytic leukaemia
KW - Gene transfer
UR - http://www.scopus.com/inward/record.url?scp=27244433608&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=27244433608&partnerID=8YFLogxK
U2 - 10.1111/j.1365-2141.2005.05699.x
DO - 10.1111/j.1365-2141.2005.05699.x
M3 - Article
C2 - 16156858
AN - SCOPUS:27244433608
VL - 130
SP - 878
EP - 889
JO - British Journal of Haematology
JF - British Journal of Haematology
SN - 0007-1048
IS - 6
ER -