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The alternative transcript of CD79b is overexpressed in B-CLL and inhibits signaling for apoptosis

The alternative transcript of CD79b is overexpressed in B-CLL and inhibits signaling for apoptosis
The alternative transcript of CD79b is overexpressed in B-CLL and inhibits signaling for apoptosis
The B-cell receptor (BCR) for antigen is composed of surface immunoglobulin (sIg), which provides antigen specificity, and a noncovalently associated signaling unit, the CD79a/b heterodimer. Defects in CD79 can influence both BCR expression and signaling and may explain why cells from certain malignancies, such as B-chronic lymphocytic leukemia (B-CLL), often express diminished and inactive BCR. Recently, an alternative transcript of CD79b (Delta CD79b) has been reported that is up-regulated in B-CLL and may explain this diminished BCR expression. Here we assess the expression of Delta CD79b in B-CLL and other lymphoid malignancies and investigate its function. High relative expression of Delta CD79b was confirmed in most cases of B-CLL and found in 6 of 6 cases of splenic lymphomas with villous lymphocytes (SLVLs) and hairy cell leukemia. In a range of Burkitt lymphoma cell lines, expression of Delta CD79b was relatively low but correlated inversely with the ability of the BCR to signal apoptosis when cross-linked by antibody (Ab). Interestingly, when Ramos-EHRB cells, which express low Delta CD79b, were transfected with this transcript, they were transformed from being sensitive to anti-Fcµ-induced apoptosis to being highly resistant. Although Delta CD79b was expressed as protein, its overexpression did not reduce the level of cell surface BCR. Finally, we showed that the inhibitory activity of Delta CD79b depended on an intact leader sequence to ensure endoplasmic reticulum (ER) trafficking and a functional signaling immunoreceptor tyrosine-based activation motif (ITAM) in its cytoplasmic tail. These results point to Delta CD79b being a powerful modulator of BCR signaling that may play an important role in normal and malignant B cells. (Blood. 2002;100:3068-3076)
0006-4971
3068-3076
Cragg, Mark S.
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Chan, H.T. Claude
b109c93f-7e9a-44ee-ad12-da757b1b11fc
Fox, Matthew D.
99fc270e-b64d-4e4f-87ea-5da550a19b44
Tutt, Alison
46ce577b-aea1-412d-84ea-fc4dab794469
Smith, Aaimée
efe30c26-f9c8-49d1-ab2f-ba72e59a7938
Oscier, David G.
c2620a1d-25bb-48f7-9651-f5d023636381
Hamblin, Terry J.
57389613-7900-48fd-b3e6-8ca8fbdceccb
Glennie, Martin J.
9f6f0eff-4560-48c2-80cd-0ec116110ded
Cragg, Mark S.
ec97f80e-f3c8-49b7-a960-20dff648b78c
Chan, H.T. Claude
b109c93f-7e9a-44ee-ad12-da757b1b11fc
Fox, Matthew D.
99fc270e-b64d-4e4f-87ea-5da550a19b44
Tutt, Alison
46ce577b-aea1-412d-84ea-fc4dab794469
Smith, Aaimée
efe30c26-f9c8-49d1-ab2f-ba72e59a7938
Oscier, David G.
c2620a1d-25bb-48f7-9651-f5d023636381
Hamblin, Terry J.
57389613-7900-48fd-b3e6-8ca8fbdceccb
Glennie, Martin J.
9f6f0eff-4560-48c2-80cd-0ec116110ded

Cragg, Mark S., Chan, H.T. Claude, Fox, Matthew D., Tutt, Alison, Smith, Aaimée, Oscier, David G., Hamblin, Terry J. and Glennie, Martin J. (2002) The alternative transcript of CD79b is overexpressed in B-CLL and inhibits signaling for apoptosis. Blood, 100 (9), 3068-3076. (doi:10.1182/blood.V100.9.3068).

Record type: Article

Abstract

The B-cell receptor (BCR) for antigen is composed of surface immunoglobulin (sIg), which provides antigen specificity, and a noncovalently associated signaling unit, the CD79a/b heterodimer. Defects in CD79 can influence both BCR expression and signaling and may explain why cells from certain malignancies, such as B-chronic lymphocytic leukemia (B-CLL), often express diminished and inactive BCR. Recently, an alternative transcript of CD79b (Delta CD79b) has been reported that is up-regulated in B-CLL and may explain this diminished BCR expression. Here we assess the expression of Delta CD79b in B-CLL and other lymphoid malignancies and investigate its function. High relative expression of Delta CD79b was confirmed in most cases of B-CLL and found in 6 of 6 cases of splenic lymphomas with villous lymphocytes (SLVLs) and hairy cell leukemia. In a range of Burkitt lymphoma cell lines, expression of Delta CD79b was relatively low but correlated inversely with the ability of the BCR to signal apoptosis when cross-linked by antibody (Ab). Interestingly, when Ramos-EHRB cells, which express low Delta CD79b, were transfected with this transcript, they were transformed from being sensitive to anti-Fcµ-induced apoptosis to being highly resistant. Although Delta CD79b was expressed as protein, its overexpression did not reduce the level of cell surface BCR. Finally, we showed that the inhibitory activity of Delta CD79b depended on an intact leader sequence to ensure endoplasmic reticulum (ER) trafficking and a functional signaling immunoreceptor tyrosine-based activation motif (ITAM) in its cytoplasmic tail. These results point to Delta CD79b being a powerful modulator of BCR signaling that may play an important role in normal and malignant B cells. (Blood. 2002;100:3068-3076)

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Published date: 1 November 2002
Additional Information: Plenary paper

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Local EPrints ID: 26258
URI: http://eprints.soton.ac.uk/id/eprint/26258
ISSN: 0006-4971
PURE UUID: 4eb9838a-d405-4bc4-9e0f-18ec88d55751
ORCID for Mark S. Cragg: ORCID iD orcid.org/0000-0003-2077-089X

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Date deposited: 21 Apr 2006
Last modified: 17 Dec 2019 01:56

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Author: Mark S. Cragg ORCID iD
Author: H.T. Claude Chan
Author: Matthew D. Fox
Author: Alison Tutt
Author: Aaimée Smith
Author: David G. Oscier
Author: Terry J. Hamblin

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