Preferential expansion upon boosting of cross-reactive 'pre-existing' switched memory B cells that recognize the SARS-CoV-2 Omicron variant Spike protein

In previously unvaccinated and uninfected individuals, non-RBD SARS-CoV-2 spike-specific B cells were prominent in two distinct, durable, resting, cross-reactive, “pre-existing” switched memory B cell compartments. While pre-existing RBD-specific B cells were extremely rare in uninfected and unvaccinated individuals, these two pre-existing switched memory B cell compartments were molded by vaccination and infection to become the primary source of RBD-specific B cells that are triggered by vaccine boosting. The frequency of wild-type RBD-binding memory B cells that cross-react with the Omicron variant RBD did not alter with boosting. In contrast, after a boost, B cells recognizing the full-length Omicron variant spike protein expanded, with pre-existing resting memory B cells differentiating almost quantitatively into effector B cell populations. B cells derived from “ancient” pre-existing memory cells and that recognize the full-length wild-type spike with the highest avidity after boosting are the B cells that also bind the Omicron variant spike protein.Abstract Figure