IgM memory B cells generated during bacterial infection are required for secondary IgG responses to antigenic challenge (43.2)

Abstract

Abstract Immunological memory was long considered to be harbored in B cells that express high affinity class-switched IgG. More recently, IgM memory B cells have been identified following immunization with nominal antigens and adjuvants. Based on the expression of CD11c, we have identified a large population of such cells using a natural model of infection by the bacterium Ehrlichia muris. These CD11c+ IgM memory cells exhibit phenotypic characteristics of memory B cells, including expression of CD73, CD11b, and PD-L2. In addition, these CD11c+ IgM memory cells lack expression of CD138, are largely quiescent, and have accumulated somatic mutations. Although these cells did not proliferate or secrete antibody ex vivo, they produced antigen-specific IgM upon in vitro stimulation with mitogens. Furthermore, in vivo depletion abrogated the IgG recall response to specific antigenic challenge. Our findings are consistent with previous data demonstrating that IgM memory cells undergo class switch recombination and affinity maturation following re-encounter with cognate antigen. We propose that these CD11c+ IgM memory B cells are responsible for the IgG produced following secondary challenge in ehrlichial infection, and likely function to provide greater flexibility to variant antigenic challenges.