autologous blood and marrow transplantation - Blog Science ...

672 Chapter 14: Radioimmunotherapy
a3
a1-cc2
C u3 C H3
Figure 5. X-ray solution of FcRB:Fc co-crystals. Lying-down configuration with 2:1
FcRB:Fc complexes are shown with a view looking parallel to the membrane. Contacts are
observed between the al-a2 domains and CH3-CH2 and between the f22m and CH2 of the
first FcRB, with lesser contacts between the amino terminus of CH2 and the second FcRB in
the receptor dimer. In this configuration, the complete IgG lies with Fab arms parallel to the
plane of the membrane. The IgG interaction with monomer vs. dimer FcRB on or in cells is
unresolved and remains a matter for investigation. Figure provided by Dr. P. Bjorkman.
activity of that tissue (Telleman P, Junghans RP, manuscript submitted). To date,
there is no evidence for an FcRn-like IgG transport activity in adult animals.
The Brambell receptor is composed of an MHC class I-related heavy chain and
a (32m light chain. 7
Crystal structures by Bjorkman and co-workers showed
contacts of Fc with nongroove domains of the FcRB class I-related heavy chain
and other contacts with the P2m light chain (Fig. 5). 12
Fc histidines were involved
in the contacts that explained the pH dependence of the binding, corroborated
independently by Ward, Ghetie, and co-workers using molecular and pharmacokinetic
techniques. 13
Extensive immuno-electron microscopy by Rodewald and coworkers
showed that FcRB expression is predominantly in the endosomes and in
the associated communication channels of the cell, with little or no surface
expression, depending on the cell type. 11415
Confirming the earlier proposed localization of the protection receptor, the
FcRB was shown to be most heavily expressed in the vascular endothelium by
immunostaining and mRNA expression. 1,1617
Given the enormous surface area of
this "tissue" (1000 m 2
), the ongoing pinocytotic activity sums to account for the
major catabolism of plasma proteins that are not renally filtered. In mice from
"clean" facilities with typically low IgG levels, the FcRp accounts for a near
tenfold reduction in the catabolic rate of IgG relative to albumin, a nonprotected