Fig. 4. Memory B cell subset development and function.

a | During an immune response, memory B cells emerging from the early germinal centre (GC) response are predominantly CD80⁻PDL2⁻. As the GC response matures, memory B cells begin to express PDL2 and CD80, with the memory B cells emerging from the late GC response predominantly being CD80⁺PDL2⁺. b | Upon antigen re-encounter, CD80⁻PDL2⁻ memory B cells predominantly differentiate into GC B cells, CD80⁻PDL2⁺ memory B cells differentiate into either GC B cells or plasma cells and CD80⁺PDL2⁺ memory B cells differentiate into plasma cells. c | A memory B cell population that is skewed towards CD80⁻PDL2⁻ memory B cells would be predisposed to differentiate into GC B cells upon antigen re-encounter. This response would promote the development of neutralizing antibodies to variant viruses but would generate a delayed response to wild-type viruses. d | A memory B cell population that is skewed towards CD80⁺PDL2⁺ memory B cells would be predisposed to differentiate into plasma cells upon antigen re-encounter. This response would promote the rapid clearance of wild-type viruses but would result in a delay in the induction of antibodies capable of neutralizing variant viruses. The dotted line in the plots on the right in parts c and d indicates the viral load necessary to enable spread of the virus to uninfected individuals. T_FH cell, follicular helper T cell.