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Memory B cells are biased towards terminal differentiation: a strategy that may prevent repertoire freezing.

Arpin C, Banchereau J, Liu YJ - J. Exp. Med. (1997)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Schering-Plough, Laboratory for Immunological Research, 69571 Dardilly, France.

ABSTRACT
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.

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. CD40L inhibits Ig  production during secondary  cultures in a dose-dependent  fashion. The culture conditions  are the same as described in Fig.  3. (A) Total IgG + IgA + IgM  production from 106 cells of naive (closed circles) and of memory  B cell cultures (open circles). (B) IgA  production. (C) IgG production. (D) IgM production. Each  circle (closed and open correspond to naive and memory cell  cultures, respectively) represents  an individual value. Mean values  are linked (plain and dotted lines  represent naive and memory cell  cultures, respectively). Standard  deviations are vertical bars.
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Figure 4: . CD40L inhibits Ig production during secondary cultures in a dose-dependent fashion. The culture conditions are the same as described in Fig. 3. (A) Total IgG + IgA + IgM production from 106 cells of naive (closed circles) and of memory B cell cultures (open circles). (B) IgA production. (C) IgG production. (D) IgM production. Each circle (closed and open correspond to naive and memory cell cultures, respectively) represents an individual value. Mean values are linked (plain and dotted lines represent naive and memory cell cultures, respectively). Standard deviations are vertical bars.

Mentions: Increasing the number of CD40L molecules available in the cultures not only inhibited the plasma cell generation, but also the secretion of Igs (Fig. 4 A). Furthermore, in all culture conditions, memory B cells produced more total Igs than naive B cells (Fig. 4 A). With regard to secreted isotype, although naive and memory B cells produced comparable levels of IgM (Fig. 4 D), memory cells, as expected, produced considerably more IgG and IgA (Fig. 4, B and C).


Memory B cells are biased towards terminal differentiation: a strategy that may prevent repertoire freezing.

Arpin C, Banchereau J, Liu YJ - J. Exp. Med. (1997)

. CD40L inhibits Ig  production during secondary  cultures in a dose-dependent  fashion. The culture conditions  are the same as described in Fig.  3. (A) Total IgG + IgA + IgM  production from 106 cells of naive (closed circles) and of memory  B cell cultures (open circles). (B) IgA  production. (C) IgG production. (D) IgM production. Each  circle (closed and open correspond to naive and memory cell  cultures, respectively) represents  an individual value. Mean values  are linked (plain and dotted lines  represent naive and memory cell  cultures, respectively). Standard  deviations are vertical bars.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2199043&req=5

Figure 4: . CD40L inhibits Ig production during secondary cultures in a dose-dependent fashion. The culture conditions are the same as described in Fig. 3. (A) Total IgG + IgA + IgM production from 106 cells of naive (closed circles) and of memory B cell cultures (open circles). (B) IgA production. (C) IgG production. (D) IgM production. Each circle (closed and open correspond to naive and memory cell cultures, respectively) represents an individual value. Mean values are linked (plain and dotted lines represent naive and memory cell cultures, respectively). Standard deviations are vertical bars.
Mentions: Increasing the number of CD40L molecules available in the cultures not only inhibited the plasma cell generation, but also the secretion of Igs (Fig. 4 A). Furthermore, in all culture conditions, memory B cells produced more total Igs than naive B cells (Fig. 4 A). With regard to secreted isotype, although naive and memory B cells produced comparable levels of IgM (Fig. 4 D), memory cells, as expected, produced considerably more IgG and IgA (Fig. 4, B and C).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Schering-Plough, Laboratory for Immunological Research, 69571 Dardilly, France.

ABSTRACT
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.

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