Activation of the local Bcell system

Peyer's patches are the best studied MALT structures and start to develop in fetal life (Cornes, 1965; Husband and Gleeson, 1990), with discrete T- and B-cell areas being apparent as early as 19 weeks of gestation (Spencer and MacDonald, 1990). The primary lymphoid follicles seem to be generated around follicular dendritic cells (FDCs). However, lymphoid hyperplasia, with secondary follicles containing germinal centres (signifying B-cell activation), does not occur until shortly after birth (Bridges et al., 1959; Spencer et al., 1986a; Gebbers and Laissue, 1990); this reflects the dependency of MALT on exogenous environmental stimulation. Furthermore, animal studies have shown an absence of secondary follicles in Peyer's patches of germ-free mice (Parrott, 1976). The germinal-centre B-cells express small amounts of membrane IgA, along with less IgM or IgG (Butcher et al., 1982). Such isotype skewing reflects differentiation to precursors for IgA-producing cells. The drive for isotype switching towards IgA, together with J-chain expression, in B-cells is much more evident in Peyer's patches than in other MALT structures, but the reasons for this are unclear (Brandtzaeg et al., 1999a, b). The combination of IgA and J-chain production is a prerequisite for the generation of SIgA antibodies (Fig. 14.2).

The retarded post-natal immune activation of MALT parallels the functionally decreased systemic immunocompetence in the newborn period (MacDonald and Spencer, 1993; Holt, 1995; Holt and Jones, 2000). Thus, peripheral CD4+ T-cells of infants show a reduced capacity for the production of interferon (IFN)-7 (Taylor and Bryson, 1985; Holt et al., 1992) and IL-4 (Lewis et al., 1991), as well as for B-cell help (Splawski and Lipsky, 1991; MacDonald and Spencer, 1993). One reason might be that there are relatively few circulating memory (CD45RO + ) T-cells in infancy. Interestingly, the responsiveness of neonatal naive (CD45RA+) T-cells does not differ significantly from that of virgin counterparts in adults, and more recent animal studies suggest that the chief explanation for the apparent immunological immaturity is to be found in a deficient APC function (Ridge et al., 1996). Thus, in the neonate macrophages, DCs and B-cells are all unable to deliver adequate co-stimulatory signals to naive T-cells (Lu et al., 1979; Taylor and Bryson, 1985; Morris et al., 1992; Ridge et al., 1996).

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