IgM⁺and IgM^-memory B cells represent heterogeneous populations capable of producing class-switched antibodies and germinal center B cells upon re-challenge withP. yoelii

Abstract

Memory B cells (MBCs) are essential for maintaining long-term humoral immunity to infectious organisms, including Plasmodium. MBCs are a heterogeneous population whose function can be dictated by isotype or expression of particular surface proteins. Here, aided by the use of antigen-specific B cell tetramers, MBC populations were evaluated to discern their phenotype and function in response to infection with a non-lethal strain of P. yoelii. Infection of mice with P. yoelii 17X resulted in the production of three predominant MBC populations: somatically hypermutated isotype-switched (swIg+) and IgM+ MBCs that co-expressed CD73 and CD80, and CD73-CD80- unmutated swIg+ B cells. Re-challenge experiments indicated that IgG-producing cells dominated the recall response with minimal induction of IgM-secreting cells. Furthermore, using fluorescent protein expression as a surrogate for CD73 and CD80 co-expression, ZsGreen1+IgM+ MBCs gave rise to class switched IgG-producing plasmablasts that induced comparable titers of Ag-specific Abs as their swIg+ counterparts after adoptive transfer and P. yoelii infection. Moreover, ZsGreen1+ IgM+ and swIg+ MBCs gave rise to B cells with a germinal center phenotype. Together these data indicated that MBC function is not defined by immunoglobulin isotype, nor does co-expression of key surface markers limit the potential fate of MBCs after recall.