Surface IgM of CLL cells displays unusual glycans indicative of engagement of antigen in vivo
Surface IgM of CLL cells displays unusual glycans indicative of engagement of antigen in vivo
Surface IgM (sIgM) has a key influence on the clinical behavior of chronic lymphocytic leukemia (CLL). We now report that it exists in 2 forms with different N-glycosylation patterns in the mu-constant region. One glycoform is similar to normal B cells in bearing mature complex glycans common to most cell-surface glycoproteins. The other is an immature mannosylated form more characteristic of mu chains in the endoplasmic reticulum. Unmutated CLL (U-CLL) expresses a higher proportion of mannosylated surface mu chains than mutated CLL. Normal B cells express only the mature glycoform but can express the immature form after persistent engagement of sIgM, suggesting that glycan modification is a consequence of antigen exposure. CLL cells express variable proportions of the mannosylated form and can revert to the mature form after incubation in vitro. Both glycoforms are able to signal after sIgM engagement in vitro, leading to enhanced tyrosine phosphorylation. These findings support the concept that CLL cells are continuously exposed to antigen in vivo, driving the N-glycosylation pattern of expressed sIgM toward a mannosylated form, especially in U-CLL. Strikingly, this is reminiscent of follicular lymphoma, where mannosylated Ig is expressed constitutively via N-glycosylation sites in the variable region, suggesting a functional asset for this glycoform
4198-4205
Krysov, S.
e783f005-15a1-4ba3-a922-4ed387a3d335
Potter, N.K.
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Mockridge, C.I.
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Coelho, V.
7e8568c5-2e53-4cb5-8934-ca391f3d791c
Wheatley, I.
a6564fc5-68c6-476d-a3e4-e86c1be33fc4
Packham, G.
fdabe56f-2c58-469c-aadf-38878f233394
Stevenson, F.
ba803747-c0ac-409f-a9c2-b61fde009f8c
2010
Krysov, S.
e783f005-15a1-4ba3-a922-4ed387a3d335
Potter, N.K.
86a99047-494b-405b-a3f7-650c1dcd5838
Mockridge, C.I.
327aef17-4837-4f2a-a93b-3d17cd1a7f9f
Coelho, V.
7e8568c5-2e53-4cb5-8934-ca391f3d791c
Wheatley, I.
a6564fc5-68c6-476d-a3e4-e86c1be33fc4
Packham, G.
fdabe56f-2c58-469c-aadf-38878f233394
Stevenson, F.
ba803747-c0ac-409f-a9c2-b61fde009f8c
Krysov, S., Potter, N.K., Mockridge, C.I., Coelho, V., Wheatley, I., Packham, G. and Stevenson, F.
(2010)
Surface IgM of CLL cells displays unusual glycans indicative of engagement of antigen in vivo.
Blood, 115 (21), .
(doi:10.1182/blood-2009-12-254847).
(PMID:20237321)
Abstract
Surface IgM (sIgM) has a key influence on the clinical behavior of chronic lymphocytic leukemia (CLL). We now report that it exists in 2 forms with different N-glycosylation patterns in the mu-constant region. One glycoform is similar to normal B cells in bearing mature complex glycans common to most cell-surface glycoproteins. The other is an immature mannosylated form more characteristic of mu chains in the endoplasmic reticulum. Unmutated CLL (U-CLL) expresses a higher proportion of mannosylated surface mu chains than mutated CLL. Normal B cells express only the mature glycoform but can express the immature form after persistent engagement of sIgM, suggesting that glycan modification is a consequence of antigen exposure. CLL cells express variable proportions of the mannosylated form and can revert to the mature form after incubation in vitro. Both glycoforms are able to signal after sIgM engagement in vitro, leading to enhanced tyrosine phosphorylation. These findings support the concept that CLL cells are continuously exposed to antigen in vivo, driving the N-glycosylation pattern of expressed sIgM toward a mannosylated form, especially in U-CLL. Strikingly, this is reminiscent of follicular lymphoma, where mannosylated Ig is expressed constitutively via N-glycosylation sites in the variable region, suggesting a functional asset for this glycoform
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Published date: 2010
Organisations:
Cancer Sciences
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Local EPrints ID: 73311
URI: http://eprints.soton.ac.uk/id/eprint/73311
ISSN: 0006-4971
PURE UUID: 64ca7803-f396-4049-84c0-33fec5ed9f2e
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Date deposited: 04 Mar 2010
Last modified: 14 Mar 2024 02:44
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Author:
S. Krysov
Author:
C.I. Mockridge
Author:
V. Coelho
Author:
I. Wheatley
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