Biology Reference
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cleared, although FDC retain Ag trapped into long-lived immune complexes at
their surface. Several groups have provided strong evidence for the continuing
involvement of Ag in the maintenance of the long-lived plasma cell pool.
In addition to the CD19, CD20, CD22, and CD40 antigens expressed by
most mature B cells, each B-cell subset is characterized by a set of markers and
a precise histological location within B-cell follicles. In lymphoid tissue, naive
(Ag-inexperienced) B cells make up the primary follicles and the mantle zone
of secondary follicles. These resident naive B cells are surface Ig (SIg)M high ,
SIgD ,CD44 high , CD38 ÿ , and a proportion of them also express CD23 and
CD5 (Liu et al., 1994). Within GC, B cells from the dark and light zones are
similarly CD38 high ,CD20 ,CD44 low , CD95 , and bcl2 ÿ . They di¨er in their
expression of SIg, CD10, and CD77: centroblasts are SIg ÿ ,CD10 , and
CD77 , whereas centrocytes express SIg (M, A, E, and G) but not CD10 and
CD77. B cells from the dark and light zones also di¨er in their expression of
the intracytoplasmic Ki67 antigen and surface B7 molecules: CD80 is strongly
expressed in the dark zone (centroblasts, CD86 low , Ki67 ) whereas CD86 is
mainly expressed in the light zone (centrocytes, CD80 low , Ki67 ÿ ) ( Vyth Dreese
et al., 1995). Memory B cells strongly express commutated SIg, CD44, and
CD20 antigens but are CD38 low and CD10 ÿ , whereas plasmablasts, which ex-
press cytoplasmic Ig, are CD38 high and CD20 low . CD62L (l-selectin) expres-
sion is also a valuable marker for recirculating naive and memory B cells. Two
markers, CD27 and CD148, have been recently shown to identify memory B
cells (Tangye et al., 1998) because only CD27 B cells seem to be able to pro-
duce commutated Ig (Agematsu et al., 1997). CD27 is also expressed by a
fraction of GC B cells, which might limit its use in the characterization of
lymphoid organ subsets (van Oers et al., 1993).
Cytokines are also key elements in B-cell proliferation, survival, and di¨er-
entiation. Interleukin (IL)-4, and to a lesser extent IL-13, act as growth factors
for BCR- or CD40-activated naive and memory B cells and rescue GC B cells
by inducing Bcl-xL expression (Tuscano et al., 1996). IL-4 is locally produced
by Ag-speci®c T cells present in the apical zone of the GC ( Flynn et al., 1998).
IL-4 and IL-13 decrease CD126 expression (gp80 IL-6R) but increase the pro-
duction of IL-6 by activated B cells. IL-4 and IL-13 are also indispensable for
the switching of naive (SIgD SIgM ) B cells to give SIgE- and SIgG4-positive
cells and for the production of IgE and IgG4 in humans. IL-10 and IL-6 sup-
port the di¨erentiation of switched B cells of all isotypes. In combination with
transforming growth factor ( TGF )-b, IL-10 also drives isotype switching
toward SIgG1, SIgG3, and SIgA1, the production of SIgA2 requiring direct
interaction between DC and B cells ( Wykes et al., 1998). Recent data suggest
that IL-6 acts as a growth and survival factor for plasmablasts (CD38 high ,
CD126 high , CD138 ÿ ), increasing the pool of early plasmocytes (CD38 high ,
CD138 ). IL-6 provides a signal for survival by increasing the expression of two
antiapoptotic molecules, Bcl- xL and Mcl1 (Puthier et al., 1999). Unlike IL-6,
IL-2 is a growth factor for B lymphoblasts and increases the number of plas-
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