The bovine IgG1 and IgG2 isotypes exhibit large differences in effector functions. To examine the structural basis for this, the 12-domain structures of IgG1 and IgG2 were investigated by pulsed neutron scattering using a recently developed camera LOQ. This method reports on the average relative disposition in solution of the Fab and Fc fragments in IgG. The radii of gyration (RG) were found to be similar at 5.64 and 5.71 nm for IgG1 and IgG2 respectively in 100% 2H2O buffers. The two cross-sectional radii of gyration (RXS) were also similar at 2.38-2.41 and 0.98-1.02 nm. Similar values were obtained for porcine IgG. Both bovine IgG1 and IgG2 possess similar overall solution structures, despite sequence differences at the hinge region at the centre of their structures. An automated computer survey of possible IgG structures was developed, in which coordinates for the two Fab fragments were displaced in a two-dimensional plane relative to those of the Fc fragment in 0.25 nm steps. The scattering curves calculated from these structures were found to be sensitive to relative displacements of the three fragments, but not on their rotational orientation about their longest axes. Good agreement with the solution scattering data was obtained with a planar IgG model in which the C-terminus of the CH1 domain of Fab was 3.6 nm from the N-terminus of Fc in both IgG1 and IgG2, with a precision of 0.7 nm. Energy refinement showed that this spatial separation is compatible with the hinge sequences of bovine IgG1 and IgG2. The results show that multidomain protein structures can be modelled using LOQ data, and that a long hinge sequence does not necessarily reflect a large distance between Fab and Fc. The steric accessibility of Fc sites for interactions with cell-surface Fc receptors and C1q of complement is shown to be generally similar for IgG1 and IgG2, and the difference in effector function between IgG1 and IgG2 is probably based on deletions in the IgG2 hinge sequence.

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In sheep the basal concentration of LH in jugular vein plasma was significantly higher during the first 50 days of gestation in late pregnancy or at parturition. The pituitary response to a single i.v. injection of 200 microng synthetic LH-RH was determined at different stages of gestation and compared with that of anoestrous and cyclic sheep. Pituitary response to LH-RH decreased progressively with advancing gestation: by 56 days after mating the response had declined to 35% and by parturition to 14% of the value in anoestrous sheep. The pituitary response to LH-RH increased after parturition and the pattern of recovery differed in non-lactating and lactating sheep. By 63 days postpartum the response to LH-RH in non-lactating and lactating animals had returned to values similar to those in sheep during anoestrus and sheep during the luteal phase of the oestrous cycle. A decrease in pituitary responsiveness during pregnancy was associated with a decrease in pituitary content of LH. The quantity of LH released in response to a standard injection of LH-RH was linearly related to pituitary LH content.

No abstract

Thymectomy in neonatal pigs results in marked lymphopenia. Surface Ig immunofluorescence, Fc rosettes and SRBC rosettes have been used to identify blood lymphocyte subpopulations. There was no marked reduction in numbers of cells in these subpopulations after thymectomy, although their proportion increased. This change was explained by a 90% reduction in ‘null’ lymphocytes, defined as those lacking slg and Dextran SRBC receptor, which comprised 30–45% of blood lymphocytes.