Higher-order immunoglobulin repertoire restrictions in CLL: the illustrative case of stereotyped subsets 2 and 169
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F21%3A00074376" target="_blank" >RIV/65269705:_____/21:00074376 - isvavai.cz</a>
Alternative codes found
RIV/00216224:14740/21:00124275
Result on the web
<a href="https://ashpublications.org/blood/article-abstract/137/14/1895/464428/Higher-order-immunoglobulin-repertoire?redirectedFrom=fulltext" target="_blank" >https://ashpublications.org/blood/article-abstract/137/14/1895/464428/Higher-order-immunoglobulin-repertoire?redirectedFrom=fulltext</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1182/blood.2020005216" target="_blank" >10.1182/blood.2020005216</a>
Alternative languages
Result language
angličtina
Original language name
Higher-order immunoglobulin repertoire restrictions in CLL: the illustrative case of stereotyped subsets 2 and 169
Original language description
Chronic lymphocytic leukemia (CLL) major stereotyped subset 2 (IGHV3-21/IGLV3-21, similar to 2.5% of all cases of CLL) is an aggressive disease variant, irrespective of the somatic hypermutation (SHM) status of the clonotypic IGHV gene. Minor stereotyped subset 169 (IGHV3-48/IGLV3-21, similar to 0.2% of all cases of CLL) is related to subset 2, as it displays a highly similar variable antigen-binding site. We further explored this relationship through next-generation sequencing and crystallographic analysis of the clonotypic B-cell receptor immunoglobulin. Branching evolution of the predominant clonotype through intraclonal diversification in the context of ongoing SHM was evident in both heavy and light chain genes of both subsets. Molecular similarities between the 2 subsets were highlighted by the finding of shared SHMs within both the heavy and light chain genes in all analyzed cases at either the clonal or subclonal level. Particularly noteworthy in this respect was a ubiquitous SHM at the linker region between the variable and the constant domain of the IGLV3-21 light chains, previously reported as critical for immunoglobulin homotypic interactions underlying cell-autonomous signaling capacity. Notably, crystallographic analysis revealed that the IGLV3-21-bearing CLL subset 169 immunoglobulin retains the same geometry and contact residues for the homotypic intermolecular interaction observed in subset 2, including the SHM at the linker region, and, from a molecular standpoint, belong to a common structural mode of autologous recognition. Collectively, our findings document that stereotyped subsets 2 and 169 are very closely related, displaying shared immunoglobulin features that can be explained only in the context of shared functional selection.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30205 - Hematology
Result continuities
Project
<a href="/en/project/LQ1601" target="_blank" >LQ1601: CEITEC 2020</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Blood
ISSN
0006-4971
e-ISSN
—
Volume of the periodical
137
Issue of the periodical within the volume
14
Country of publishing house
US - UNITED STATES
Number of pages
10
Pages from-to
1895-1904
UT code for WoS article
000646123500011
EID of the result in the Scopus database
2-s2.0-85103767275