Germinal centers in human lymph nodes contain reactivated memory B cells.
To reveal migration trails of antigen-responsive B cells in lymphoid tissue, we analyzed immunoglobulin (Ig)M-V(H) and IgG-V(H) 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.
Bende
Richard J
RJ
Department of Pathology, Academic Medical Center, 1105 AZ Amsterdam, Netherlands.
van Maldegem
Febe
F
Triesscheijn
Martijn
M
Wormhoudt
Thera A M
TA
Guijt
Richard
R
van Noesel
Carel J M
CJ
D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002455:Cell Division; D002999:Clone Cells; D005784:Gene Amplification; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007075:Immunoglobulin M / Q000235:genetics; D007156:Immunologic Memory; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation; D013601:T-Lymphocytes / Q000276:immunology; D014158:Transcription, Genetic
D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M