© The Rockefeller University Press, 0022-1007/1997/2/563/ $5.00
The Journal of Experimental Medicine, Volume 185, Number 3, February 3, 1997 563-572
Germinal Center Founder Cells Display Propensity for Apoptosis before Onset of Somatic Mutation
Serge Lebecque,
Odette de Bouteiller,
Christophe Arpin,
Jacques Banchereau, and
Yong-Jun Liu
From Schering-Plough, Laboratory for Immunological Research, 69571 Dardilly, France
B lymphocytes undergo affinity maturation of their antigen receptors within germinal centers. These anatomical structures develop in secondary lymphoid organs from the clonal expansion of a few antigen-specific founder B cells, whose isolation and characterization are reported here. Human germinal center founder cells express the naive B cell markers surface IgM and IgD as well as the germinal center B cell markers CD10 and CD38. They express low levels of Bcl-2, high levels of Fas, and undergo rapid apoptosis in culture. The smaller nonproliferating sIgM+IgD+CD38+ B cells displayed a lower level of somatic mutation in their immunoglobulin variable region genes compared with the large proliferating ones. Unmutated sIgM+IgD+CD38+ tonsillar B cells may thus represent germinal center founder cells in which the program for apoptotic cell death is triggered before the onset of somatic mutation, allowing the selection of the germline antibody repertoire at an early stage.
Address correspondence to Drs. Serge Lebecque and Yong-Jun Liu, Schering-Plough, 27 chemin des Peupliers, BP11, 69571 Dardilly, France.
C. Arpin is recipient of a grant from Fondation Narcel Nérieux (Lyon, France).
1Abbreviations used in this paper: APAAP, alkaline phosphatase-anti-alkaline phosphatase system; GC, germinal center.

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