Against an epitope, high-affinity BCR means strong signaling and vice-versa. But what does affinity mean in terms of molecular events? How does the cell know the BCR is of high-affinity? Is it crosslinking of more BCR molecules and hence more phosphorylation? Or is it longer durations of crosslinking and hence continuous signaling? Or any other mechanism?
In my opinion, BCR affinity translates into peptide-MHCII density presented on the surface of the GC B cells engaging T follicular helper cells with cognate TCR. Therefore, high affinity BCR will outcompete lower ones for binding and more efficiently present the peptide to MHCII so that they are more likely to be selected for differentiation into plasma cells or memory B cells. I don't know if BCR downstream signaling is higher with higher affinity, but my best guess is yes because we know that both BCR signaling provided by antigen and extrinsic signals provided by Tfh are important for GC B cell fate.
Thank you for the answer. I do agree that for selection by T cells, high-affinity (HA) BCRs may fetch more MHC complexes than low-affinity (LA) BCRs. But for that to happen, do you think HA B cells compete with LA B cells for the limiting resourse - the antigen? Or is it purely thermodynamically favoured since HA BCRs' interactions are more favoured?
Also, with respect to the BCR itself, I wished to know if HA would mean longer crosslinking or crosslinking of more BCR molecules? Either of these would make me question "what about monovalent antigens, then?".
To the best of my knowledge, I don't know if people have looked at BCR alone in terms of crosslinking and its downstream signaling without talking about its fate in the context of plasma cell differentiation or memory B cells differentiation or under pathological conditions such as autoimmune diseases. I don't think the antigen during a certain period of time such as infection or immunization will be a limited source because, FDC is suggested to be an important source for storage or anchor of antigens but no one has proved that. Within the same time window, I think both LA and HA will have similar access to the antigen, (and maybe because of the crosslinking, )there are some intrinsic difference due the different BCR downstream signaling caused by the affinity of the BCR so that they might have different rate of expansion, migration, etc.
It is gotta be membrane bound antigen. B cells use mechanical pulling force to test the affinity of BCRs to antigen.
If antigen is in solution, high affinity cross-link more BCR due to high on and low off rate but resolution would not be as high as antigen presented on the membrane.
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