Fig. 1

Summary of the current knowledge on the origin of and connections between classical and atypical MBCs. A Potential differentiation pathways of classical memory B cells (cMBCs) and atypical memory B cells (atMBCs). Upon antigen exposure, naïve B cells become activated and can differentiate into antibody-secreting cells (not shown) or classical MBCs. Atypical MBCs are detected after primary P. falciparum infection and may thus be derived from naïve B cells, either directly or through an intermediate cell type. It is not known whether classical MBCs can also differentiate into atypical MBCs after antigen exposure, and whether there is a difference in differentiation pathways between IgM⁺ and IgG⁺ atypical MBCs. Classical MBCs are defined by the expression of surface markers CD21 and CD27, while the majority of classical MBCs lack FcRL5⁻. Atypical MBCs are defined by the absence of CD21 and CD27. Most atypical MBCs express FcRL5 and other markers described in the main text. B FcRL5⁻ and FcRL5⁺ classical and atypical MBCs showed differences in their ability to differentiate into antibody-secreting cells when stimulated in vitro with soluble antigen and other stimuli. The relative number of antibody-secreting cells after stimulation is represented by the number of immunoglobulin molecules. These results suggest that FcRL5⁺ classical and atypical MBCs may be developmentally related