Understanding Memory B Cell Selection

TL;DR

This paper explores the evolutionary and functional reasons behind memory B cell selection, proposing it as an approximate solution to future antigen recognition and immune response optimization, supported by simulation data.

Contribution

It introduces a novel hypothesis that memory B cell selection is an optimization strategy for future immune challenges, supported by simulation evidence.

Findings

Memory B cells are selected earlier with lower affinity.

Memory B cells tend to have high affinity to mutated antigens.

No strong evidence that memory B cells outperform naive B cells in secondary responses.

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.