A New Memory CD27–IgG+ B Cell Population in Peripheral Blood Expressing VH Genes with Low Frequency of Somatic Mutation1

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BlankThe Journal of Immunology, 2006, 177: 3728-3736.

Copyright © 2006 by The American Association of Immunologists

A New Memory CD27–IgG+ B Cell Population in Peripheral Blood Expressing VH Genes

with Low Frequency of Somatic Mutation1

Jessie F. Fecteau, Geneviève Côté and Néron2

Héma-Québec, Recherche et Développement, Sainte-Foy, Quebec, Canada

In humans, up to 40% of peripheral B cells express CD27 and have hypermutated

variable regions in their Ig genes. The CD27+ B cells are considered to be

derived from germinal center following specific antigenic stimulation. Actually,

somatic hypermutation in Ig genes and CD27 expression are hallmarks of memory B

cells. However, the blood IgM+IgD+CD27+ B cells were recently associated to

splenic marginal zone B cells and proposed to be a subset distinct from germinal

center-derived memory B cells showing premutated Igs. The results presented

herein further weaken this bona fide association because B cells expressing

surface IgG, but not CD27, were found in human blood. Representing 1–4% of all

peripheral B cells and 25% of the IgG+ blood B cells, this population expressed

mutated IgG genes showing antigenic selection characteristics but with lower

mutation frequencies than that of CD27+IgG+ B cells. However, their morphology

and phenotype were similar to that of CD27+IgG+ cells. Interestingly, the

proportion of IgG2 over IgG3 transcripts was opposite in CD27–IgG+ and CD27+IgG+

cells, suggesting distinct functions or origins. Overall, these findings extend

the memory B cell reservoir beyond the CD27+ compartment and could provide

further insights into B cell disorders of unknown etiology.

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1 J.F.F. was supported by a Ph.D. fellowship from le Fond Québécois de la

Recherche sur la Nature et les Technologies and from Héma-Québec.

2 Address correspondence and reprint requests to Dr. Néron, Héma-Québec,

Recherche et Développement, 1009 route du Vallon, Sainte-Foy, Quebec G1V 5C3,

Canada. E-mail address: sonia.neron@...

3 Abbreviations used in this paper: ABC, ATP-binding cassette; MTG, MitoTracker

Green; IMGT, ImMunoGeneTics; FR, framework region; R, replacement; S, silent;

MFI, mean fluorescence intensity; FcRH4, FcR homolog 4.