First Aid, Chapter 1 Immune mechanisms, B-cell receptor and signaling Flashcards
What molecules are noncovalently associated with Igα and Igβ chains on the BCR and are required for signal transduction?
ITAMs
What is cross-linking? What receptors require cross-linking?
Recognition of the antigen by at least two receptors. BCR activation will not occur without receptor cross-linking.
When are lipid rafts formed? What do lipid rafts do?
They are formed with cross-linking. They bring the BCR and the Src family of kinases in close proximity.
What are the BCR Src kinases? What do they do?
The BCR Src kinases are Lyn, Fyn, and BTK. Like in the TCR, they phosphorylate the ITAMs, providing a docking site for Syk. These are, again, Src homology domains.
What is Syk?
ZAP-70 analog, and its phosphorylation of molecules (e.g., PLC and accessory molecules) is active in the same pathways as for transcription factor activation.
What does B-lymphocyte linker protein (BLNK) do?
when phosphorylated by Syk, it will further activate Ras and Rac, PLC, and Bruton’s tyrosine kinase (BTK).
What receptor is BTK unique to? What does it do?
BTK is unique to B lymphocytes. BTK and Syk activate PLC to break PIP2 down to IP3 and make diacylglycerol (DAG) analogous to the TCR pathway. BTK is also involved in B-lymphocyte maturation.
What does mutation in BTK produce?
Bruton’s agammaglobulinemia or X-linked agammaglobulinemia.
What is the role of CD21 (CR2)? What is the ligand for CD21? How is the ligand made?
It provides signals that enhance the BCR if the antigen is opsonized by C3b. On the surface, C3b is covalently bound to the antigen and degraded to C3d, which is the ligand for CD21.
What happens after CD21 interacts with C3d?
The CD21-CD19-CD81 complex that is expressed on the surface of B lymphocytes is brought into the BCR. CD19 has an ITAM that is phosphorylated, thus recruiting Lyn to enhance phosphorylation of the Igα and Igβ chains; it also activates IP3 kinase, which helps in BTK and PLC recruitment.