Although immune memory often lasts for life, this is not the case for certain vaccines in some individuals. We sought a mechanism for this phenomenon by studying B cell responses to phycoerythrin (PE). PE immunization of mouse strains with Ighb immunoglobulin (Ig) variable heavy chain (VH) genes elicited affinity-matured switched Ig memory B cells that declined with time, while the comparable population from an Igha strain was numerically stable. Ighb strains had larger numbers of PE-specific naive B cells and generated smaller germinal center responses and larger numbers of IgM memory cells than the Igha strain. The properties of PE-specific B cells in Ighb mice correlated with usage of a single VH that afforded high-affinity PE binding in its germline form. These results suggest that some individuals may be genetically predisposed to generate non-canonical memory B cell responses to certain antigens because of avid antigen binding via germline-encoded VH elements. Immunity induced by certain vaccines declines over time. By studying B cell responses to phycoerythrin, Pape et al. find that memory B cells can be short-lived when generated from precursors that experience unusually strong early signals through their un-mutated antigen receptors.
Bibliographical noteFunding Information:
Supported by grants from the US National Institutes of Health ( R37 AI027998 and R01 AI039614 ) to M.K.J. and the Intramural Research Program of the National Institutes of Health, National Institute on Aging to P.J.G. The authors acknowledge technical assistance from David Wu, Madeline Pape, and Jennifer Walter.
- memory B cell
- naive B cell