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B cell receptor isotypes differentially associate with cell signaling, kinetics, and outcome in chronic lymphocytic leukemia.
- Source :
-
The Journal of clinical investigation [J Clin Invest] 2022 Jan 18; Vol. 132 (2). - Publication Year :
- 2022
-
Abstract
- In chronic lymphocytic leukemia (CLL), the B cell receptor (BCR) plays a critical role in disease development and progression, as indicated by the therapeutic efficacy of drugs blocking BCR signaling. However, the mechanism(s) underlying BCR responsiveness are not completely defined. Selective engagement of membrane IgM or IgD on CLL cells, each coexpressed by more than 90% of cases, leads to distinct signaling events. Since both IgM and IgD carry the same antigen-binding domains, the divergent actions of the receptors are attributed to differences in immunoglobulin (Ig) structure or the outcome of signal transduction. We showed that IgM, not IgD, level and organization associated with CLL-cell birth rate and the type and consequences of BCR signaling in humans and mice. The latter IgM-driven effects were abrogated when BCR signaling was inhibited. Collectively, these studies demonstrated a critical, selective role for IgM in BCR signaling and B cell fate decisions, possibly opening new avenues for CLL therapy.
- Subjects :
- Animals
Female
Humans
Immunoglobulin D genetics
Immunoglobulin M genetics
Leukemia, Lymphocytic, Chronic, B-Cell genetics
Male
Mice
Mice, Knockout
Receptors, Antigen, B-Cell genetics
Signal Transduction genetics
B-Lymphocytes immunology
Immunoglobulin D immunology
Immunoglobulin M immunology
Leukemia, Lymphocytic, Chronic, B-Cell immunology
Receptors, Antigen, B-Cell immunology
Signal Transduction immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1558-8238
- Volume :
- 132
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- The Journal of clinical investigation
- Publication Type :
- Academic Journal
- Accession number :
- 34813501
- Full Text :
- https://doi.org/10.1172/JCI149308