B-Cell-Specific Myd88 L252P Expression Causes a Premalignant Gammopathy Resembling IgM MGUS.
Animals
B-Lymphocytes
/ immunology
Cell Proliferation
Cell Survival
Cells, Cultured
Gene Targeting
Genetic Predisposition to Disease
Immunoglobulin M
/ blood
Lymphocyte Activation
Mice, Inbred C57BL
Monoclonal Gammopathy of Undetermined Significance
/ blood
Myeloid Differentiation Factor 88
/ genetics
Paraproteins
/ metabolism
Phenotype
Plasma Cells
/ immunology
Point Mutation
B cell abnormalities
B cell lymphoma
IgM MGUS
IgM paraprotein
MYD88 L265P mutation
Waldenström’s macroglobulinemia
lymphomagenesis
monoclonal gammopathy of unknown significance
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2020
2020
Historique:
received:
04
09
2020
accepted:
19
10
2020
entrez:
21
12
2020
pubmed:
22
12
2020
medline:
22
6
2021
Statut:
epublish
Résumé
A highly recurrent somatic L265P mutation in the TIR domain of the signaling adapter MYD88 constitutively activates NF-κB. It occurs in nearly all human patients with Waldenström's macroglobulinemia (WM), a B cell malignancy caused by IgM-expressing cells. Here, we introduced an inducible leucine to proline point mutation into the mouse Myd88 locus, at the orthologous position L252P. When the mutation was introduced early during B cell development, B cells developed normally. However, IgM-expressing plasma cells accumulated with age in spleen and bone, leading to more than 20-fold elevated serum IgM titers. When introduced into germinal center B cells in the context of an immunization, the Myd88
Identifiants
pubmed: 33343574
doi: 10.3389/fimmu.2020.602868
pmc: PMC7747680
doi:
Substances chimiques
Immunoglobulin M
0
Myd88 protein, mouse
0
Myeloid Differentiation Factor 88
0
Paraproteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
602868Informations de copyright
Copyright © 2020 Schmidt, Sack, Graf, Winkler, Popp, Mertins, Sommermann, Kocks and Rajewsky.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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