Faculty, Staff and Student Publications
Publication Date
1-18-2022
Journal
Journal of Clinical Investigation
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.
Keywords
Animals, B-Lymphocytes, Female, Humans, Immunoglobulin D, Immunoglobulin M, Leukemia, Lymphocytic, Chronic, B-Cell, Male, Mice, Mice, Knockout, Receptors, Antigen, B-Cell, Signal Transduction, Immunoglobulins, Leukemias
DOI
10.1172/JCI149308
PMID
34813501
PMCID
PMC8759784
PubMedCentral® Posted Date
1-18-2022
PubMedCentral® Full Text Version
Post-print
Graphical Abstract
Published Open-Access
yes
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Medical Sciences Commons, Oncology Commons