The Journal of Experimental Medicine
BioLegend: Antibody Reagents
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Published online October 15, 2007
doi:10.1084/jem.20071006
The Journal of Experimental Medicine, Vol. 204, No. 11, 2655-2665
The Rockefeller University Press, 0022-1007 $30.00
© 2007 Bende et al.
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ARTICLE

 Germinal centers in human lymph nodes contain reactivated memory B cells

Richard J. Bende, Febe van Maldegem, Martijn Triesscheijn, Thera A.M. Wormhoudt, Richard Guijt, and Carel J.M. van Noesel

Department of Pathology, Academic Medical Center, 1105 AZ Amsterdam, Netherlands

CORRESPONDENCE C.J.M. van Noesel: c.j.vannoesel{at}amc.uva.nl

To reveal migration trails of antigen-responsive B cells in lymphoid tissue, we analyzed immunoglobulin (Ig)M-VH and IgG-VH transcripts of germinal center (GC) samples microdissected from three reactive human lymph nodes. Single B cell clones were found in multiple GCs, one clone even in as many as 19 GCs. In several GCs, IgM and IgG variants of the same clonal origin were identified. The offspring of individual hypermutated IgG memory clones were traced in multiple GCs, indicating repeated engagement of memory B cells in GC reactions. These findings imply that recurring somatic hypermutation progressively drives the Ig repertoire of memory B cells to higher affinities and infer that transforming genetic hits in non-Ig genes during lymphomagenesis do not have to arise during a single GC passage, but can be collected during successive recall responses.

Abbreviations used: Ag, antigen(ic); CDR3, complementarity determining region 3; CSR, class-switch recombination; FM, follicular mantle zone; GC, germinal center; IgV, Ig variable region; SHM, somatic hypermutation; TZ, T cell zone.


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