A germinal center–independent pathway generates unswitched memory B cells early in the primary response

Abstract

Memory B cells can be produced from the classical germinal center (GC) pathway or a less understood GC-independent route. We used antigen-based cell enrichment to assess the relative contributions of these pathways to the polyclonal memory B cell pool. We identified a CD38+ GL7+ B cell precursor population that differentiated directly into IgM+ or isotype-switched (sw) Ig+ memory B cells in a GC-independent fashion in response to strong CD40 stimulation. Alternatively, CD38+ GL7+ B cell precursors had the potential to become Bcl-6+ GC cells that then generated primarily swIg+ memory B cells. These results demonstrate that early IgM+ and swIg+ memory B cells are products of a GC-independent pathway, whereas later switched Ig+ memory B cells are products of GC cells.