Figure 10: Dynamic interaction between mIgG-tail and acidic phospholipids governs the enhanced activation of memory B cells.

(a) In quiescent IgG-BCR expressing memory B cells, the positively charged mIgG-tail interacts with acidic phospholipids in the inner leaflet of the plasma membrane, leading to the sequestration of the key ITT tyrosine within the membrane hydrophobic core. (b) Upon the antigen engagement, Igα- and Igβ-ITAMs are phosphorylated by Lyn, and then recruit downstream signalling molecules to induce Ca²⁺ mobilization. Meanwhile, the antigen engagement of IgG-BCRs also initially perturbs the interaction of the ITT with the PM. Such disturbance triggers the exposure of the ITT-tyrosine and the subsequent phosphorylation by Syk. Phosphorylated ITT carries extra negative charges. The charge repulsion from acidic lipids will make the pITT stably localized in cytosol to recruit Grb2, thus further enhancing the Ca²⁺ influx^16,17. (c) ITAM signalling triggers Ca²⁺ influx through CRAC channel. The accumulation of membrane-proximal Ca²⁺ can neutralize the negative charges of acidic phospholipids and thus can in turn facilitate the dissociation of mIgG-tail from the plasma membrane. Thus, all these steps in (a–c) work in an ordered manner to amplify the antigen-initiated signalling to a greater magnitude and thus contribute to the enhanced activation of IgG-BCR expressing memory B cells in comparison with the case of IgM-BCR expressing mature naïve B cells.