13 antigen signalling in B cell lymphoma Flashcards
Why do many B-cell neoplasms retain surface BCR expression despite IG-associated translocations?
Ongoing antigen selection for functional BCR
SHM profiles show non-random mutations, suggesting selection pressure
What is the significance of IG sequence heterogeneity in B-cell lymphomas?
Indicates ongoing somatic hypermutation (SHM) and antigen-mediated selection.
How does SHM suggest selection for functional antigen receptors?
CDR regions have a high concentration of mutations
FR regions have fewer mutations → preserving BCR function
Which B-cell neoplasms express stereotyped BCRs?
Chronic Lymphocytic Leukaemia (CLL)
Mantle Cell Lymphoma (MCL)
What are stereotyped BCRs?
BCRs with highly homologous sequences, including:
Same V/D/J segment usage
Similar CDR3 sequences
Identical heavy-light chain pairings
What percentage of CLL cases carry just 19 different CDR3 sequences?
12% – an extremely non-random distribution.
What does stereotyped BCR usage in lymphomas suggest?
Recognition of common antigens driving B-cell expansion.
Which B-cell lymphomas express BCRs that recognise autoantigens?
Subset of CLL
Subset of MCL (LRPAP1)
Subset of MALT lymphoma (Sjogren’s syndrome)
Subsets of DLBCL (SAMD14, ARS2)
Which B-cell neoplasms recognise foreign pathogenic antigens?
NLPHL (M. catarrhalis)
MALT lymphoma (e.g., Helicobacter pylori)
What is MALT lymphoma?
An indolent lymphoma arising from chronic inflammation or infection.
Which infections are linked to MALT lymphoma?
Helicobacter pylori (stomach)
Borrelia burgdorferi (skin)
Chlamydia psittaci (orbit)
Which autoimmune diseases are associated with MALT lymphoma?
Sjogren’s syndrome (salivary glands)
Autoimmune thyroiditis (thyroid)
How can gastric MALT lymphoma be treated?
Antibiotic therapy to eradicate Helicobacter pylori.
What is the role of BCR signalling in B-cell lymphomas?
Drives proliferation and survival
Some lymphomas require chronic antigen stimulation
What is Lyn, and what is its role in BCR signalling?
Lyn is a kinase that provides negative feedback to regulate BCR signalling.
What is chronic active BCR signalling?
A condition where BCR signalling remains constitutively active, even without antigen binding.
Which lymphoma subtype relies on chronic active BCR signalling?
ABC-DLBCL (Activated B-Cell Diffuse Large B-Cell Lymphoma).
Which genetic alterations affect BCR signalling in DLBCL?
Mutations in CARD11 → NF-κB activation
Mutations in BTK → Constitutive signalling
Mutations in CD79A/B → Hyperactive BCR
What are the key principles of B-cell neoplasia related to BCR signalling?
Many B-cell lymphomas retain normal B-cell properties
Antigen receptor signalling is essential for survival in some lymphomas
Why is BCR signalling a therapeutic target in B-cell lymphomas?
Many lymphomas depend on BCR activation
Blocking key signalling molecules can disrupt tumour survival
Which inhibitors target BCR signalling in B-cell lymphomas?
BTK inhibitors
NF-κB inhibitors
BCL2 inhibitors
SYK inhibitors
PI3K inhibitors
What is a major BTK inhibitor used in lymphoma treatment?
Ibrutinib (a Bruton’s tyrosine kinase (BTK) inhibitor).
How does ibrutinib work?
Blocks BTK-dependent BCR signalling, reducing tumour survival.
What is a major PI3K inhibitor used in lymphoma treatment?
Idelalisib, which blocks PI3K-dependent survival pathways.
How does precision medicine improve DLBCL treatment?
Uses molecular profiling to predict:
Lymphoma subtype
Best targeted therapy
What is the key principle of precision medicine in B-cell lymphoma?
Understanding the molecular basis of lymphoma leads to new targeted treatments.
