© The Rockefeller University Press, 0022-1007/1997/9/931/ $5.00
The Journal of Experimental Medicine, Volume 186, Number 6, September 15, 1997 931-940
Memory B Cells Are Biased Towards Terminal Differentiation: A Strategy That May Prevent Repertoire Freezing
Christophe Arpin,
Jacques Banchereau, and
Yong-Jun Liu
From Schering-Plough, Laboratory for Immunological Research, 69571 Dardilly, France
Isolation of large numbers of surface IgD+CD38– naive and surface IgD–CD38– memory B cells allowed us to study the intrinsic differences between these two populations. Upon in vitro culture with IL-2 and IL-10, human CD40–activated memory B cells undergo terminal differentiation into plasma cells more readily than do naive B cells, as they give rise to five- to eightfold more plasma cells and three- to fourfold more secreted immunoglobulins. By contrast, naive B cells give rise to a larger number of nondifferentiated B blasts. Saturating concentrations of CD40 ligand, which fully inhibit naive B cell differentiation, only partially affect that of memory B cells. The propensity of memory B cells to undergo terminal plasma cell differentiation may explain the extensive extra follicular plasma cell reaction and the limited germinal center reaction observed in vivo after secondary immunizations, which contrast with primary responses in carrier-primed animals. This unique feature of memory B cells may confer two important capacities to the immune system: (a) the rapid generation of a large number of effector cells to efficiently eliminate the pathogens; and (b) the prevention of the overexpansion and chronic accumulation of one particular memory B cell clone that would freeze the available peripheral repertoire.
Address correspondence to Dr. Yong-Jun Liu, Schering-Plough, 27 chemin des Peupliers, BP 11, 69571 Dardilly Cedex, France. Phone: 33-4-72-17-27-00; FAX: 33-4-78-35-47-50; E-mail: lir{at}schering-plough.fr
C. Arpin is the recipient of a grant from Fondation Mérieux.
1 Abbreviations used in this paper: BCR, B cell receptor; CD40L, CD40 ligand; GC, germinal center; PC, plasma cell.

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