B cells spread to affinity

B cells extend like fishnets to capture and then draw in antigens, according to new research by Sebastian Fleire, Facundo Batista (Cancer Research UK London Research Institute, London, UK), and colleagues. The mechanism allows B cells to discern the affinities of the different membrane-bound antigens they encounter.

The interaction of B cell receptors with antigens gives birth to the immunological synapse, spurring B cell activation and antigen presentation to T cells if the antigen is sufficiently well suited to the B cell receptor. Batista's group examined the cellular changes that accompany the first moments of synapse formation.

The authors exposed naive B cells to lysozyme antigens with varying affinities for a B cell receptor and watched as the cells first spread, and then contracted inward, drawing in their captured antigens. The degree of B cell spreading depended on two factors: the amount of antigen detected by the B cell and its affinity toward the antigen.

The spread–contract mechanism may help the immune system select for B cells that produce the highest affinity antibodies to a specific antigen. “If you have a high-affinity interaction, you will see higher spreading,” says Batista. More antigen will thus be aggregated, which in turn will increase B cell maturation and activation.

The researchers supported their experimental results with a mathematical model in which disabling B cell spreading led to similar amounts of antigen accumulation for both low- and high-affinity antigens. With spreading, however, abundant high-affinity antigens were gathered in higher quantities.

Batista notes that, by spreading and contracting, a B cell improves its chances of eliciting T cell help. More broadly, he says, “this could be a general mechanism by which cells recognize different ligands.” T cells, for example, were recently shown to spread in a similar manner.

Reference: