Biology Reference
In-Depth Information
B-cell tra½cking. B-cell follicles from lymphoid organs appear normal in plt
mice that lack SLC and have low levels of ELC production (Vassileva et al.,
1999). In ccr7ÿ=ÿ mice, B-cell activation and migration within lymphoid
organs are abnormal. These mice spontaneously produce high levels of IgG1,
IgG2a, and IgE and have enlarged GC, showing strong and inappropriate
B-cell activation (Forster et al, 1999). Adoptive transfer experiments demon-
strated that CCR7-de®cient B cells enter into lymph nodes and Peyer's patches
with a low frequency and rapidly leave the outer periarteriolar lymphoid sheath
( PALS), a region essential for Ag-speci®c cell-cell interactions and B-cell dif-
ferentiation (Forster et al., 1999). Thus, the physiological role of CCR7 seems
to favor the establishment of e¨ective T/B interactions in delaying the release
of Ag-speci®c B cells from the PALS. ELC weakly promotes the migration of
naive B cells but induces that of BCR-activated B cells ( Ngo et al., 1998).
We have recently shown that naive and memory B cells, unlike GC and
plasmablasts, express CCR6, the receptor of macrophage in¯ammatory protein
(MIP)-3a (Krzysiek et al, 2000). Naive B cells express CCR6 but seem to be
unable to migrate in response to MIP-3a, suggesting that CCR6 is mostly in-
volved in control of the migration of memory B cells. BCR triggering of these B
cells leads to the loss of CCR6 expression and MIP-3a responsiveness, whereas
CD40 triggering or cytokine addition have no such e¨ect. In T cells, both
CCR6 expression and responsiveness to MIP-3a are restricted to the memory
pool (Sallusto et al., 1999). MIP-3a is highly expressed by in¯amed epithe-
lial cells from tonsilar crypts and subepithelial regions of intestinal and lung
mucosa, consistent with functional CCR6 receptors being preferentially ex-
pressed on memory cells ( Tanaka et al., 1999). The esssential role of the CCR6/
MIP-3a pair as a mucosa-speci®c regulator of humoral immunity and lympho-
cyte homeostasis in the intestinal mucosa has been de®nitively established in
CCR6ÿ=ÿ mice (Cook et al., 2000).
Apart from fractalkine, which has both a membrane-anchored and a soluble
form (Combadiere et al., 1998), chemokines control the migration of their tar-
get cells by activating a speci®c set of integrins and selectins. The activation
of selectins results in the attachment and rolling of cells, whereas activated
integrins control the ®rm adhesion and transendothelial migration of cells
(Cyster, 1999). For example, SLC induces the ®rm adhesion of naive T cells to
immune cell adhesion molecule (ICAM1) via b2 integrin and is a potent inducer
of the a4b7-mediated adhesion of lymphocytes to Mucosal address in cell ad-
hesion molecule (MadCAM1) expressed by high endothelial venules (HEV)
( Warnock et al., 2000). The combination of a particular set of chemokine re-
ceptors and adhesion molecules therefore confers speci®c abilities on each
cell subset to recirculate, or to interact with other cells or with the extracellu-
lar matrix. To date, little is known about the integrins and selectins used for
directing B cells to speci®c organs and to particular areas within each organ.
There is much evidence to suggest that colonization by B cells is controlled by a
di¨erent combination of chemokines and TNF-related cytokines in spleen and
lymph nodes (Gonzalez et al., 1998).
