Influenza virus-specific memory B cells are critical to mount an accelerated antibody response against subsequent influenza infections. While multiple layers of humoral memory are involved in the protection against influenza, the unique role of IgM memory B cells is largely unknown. In this study, we demonstrated that human IgM memory B cells are similar to class-switched memory B cells in their basic effector functions: the ability to proliferate and to present antigens to T cells. However, ELISPOT analysis of peripheral blood mononuclear cells revealed that the frequency of influenza-specific IgM memory B cells is 10-fold higher than that of IgG memory B cells and doesn’t readily change by seasonal vaccination. Interestingly, IgM memory B cells exhibited broad cross-reactivity against contemporary seasonal as well as pandemic strains. Serum antibody analysis showed that although the level of influenza-specific IgM was approximately 20-fold less than that of IgG, the breadth of cross-reactivity of IgM-secreting cells is broader than that of IgG counterparts. Given that a recent study in mice showed that the majority of IgM memory B cells are preferentially recruited to the ensuing secondary response, we propose a model that upon vaccination, some IgM memory B cells are directly differentiated into highly cross-reactive IgM-secreting plasmablasts to confer the host early line of cross-protection, while the rest of IgM memory B cells are recruited to the secondary response.
- Copyright © 2013 by The American Association of Immunologists, Inc.