Abstract: The mammalian adaptive immune system has evolved over millions of years to become an incredibly effective defense against foreign antigens. The adaptive immune system's humoral response creates plasma B cells and memory B cells, each with their own immunological objectives. The affinity maturation process is widely viewed as a heuristic to solve the global optimization problem of finding B cells with high affinity to the antigen. However, memory B cells appear to be purposely selected earlier in the affinity maturation process and have lower affinity. We propose that this memory B cell selection process may be an approximate solution to two optimization problems: optimizing for affinity to similar antigens in the future despite mutations or other minor differences, and optimizing to warm start the generation of plasma B cells in the future. We use simulations to provide evidence for our hypotheses, taking into account data showing that certain B cell mutations are more likely than others. Our findings are consistent with memory B cells having high-affinity to mutated antigens, but do not provide strong evidence that memory B cells will be more useful than selected naive B cells for seeding the secondary germinal centers.
Recommendations
- An analysis of B cell selection mechanisms in germinal centers
- Multi-type Galton-Watson processes with affinity-dependent selection applied to antibody affinity maturation
- A CONCERTED ACTION OF B CELL SELECTION MECHANISMS
- Antigen-driven selection in germinal centers as reflected by the shape characteristics of immunoglobulin gene lineage trees: a large-scale simulation study
- scientific article; zbMATH DE number 1057999
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