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J Exp Med. 2012 Mar 12;209(3):597-606. doi: 10.1084/jem.20111696. Epub 2012 Feb 27.

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

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Department of Microbiology, Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA.


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.

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