Margaret C Holmes

Allergy to murine antigens in a biological research insitute

Symptomatic and immunologic responses to allergens from laboratory mice were studied in a research institute. Subjects who had been exposed to mice and 50 unexposed subjects were studied by questionnaire and by prick tests with seven prevalent aeroallergens and allergens from mouse urine and pelts. Of the 121 exposed subjects, 39 (32.2%) had respiratory, ocular, or cutaneous symptoms after exposure to mice; occurrence of these symptoms correlated with positive skin tests to purified mouse urinary proteins (MUP) and pelt allergens from CBA/H mice. Serum levels of IgG antibodies correlated with the frequency of mouse exposure. In subjects with seasonal allergic rhinitis, nasal symptoms from exposure to mice, positive prick tests to MUP, and IgE antibodies to MUP were significantly more prevalent. The possibility of genetic influences on susceptibility to mouse allergy were also suggested by a negative association between the incidence of HLA-DRW6 and positive prick-test responses to urinary proteins from C57BL and BALB/c mice among the 54 subjects who were exposed to mice and tested for DR locus antigens (p = 0.05). However, no significant differences in any of the loci studied could be shown in subjects with and without nasal symptoms from exposure to mice.

Genetic investigations of autoimmune disease in mice.

The theoretical curves of E( ).) for various graphite grain radii are plotted in Figs. 2 and 3. The open circles plotted in Figs. 2 and 3 represent the extinction curve given by Boggess and Borgm.an2 including their ultraviolet observations. It is seen that the shapes of the theoretical curves for ).-1 < 3 (Figs. 2 and 3) bear a general resemblance to the observational curves in Fig. 1. There seems to bo little doubt that any of the observational curves reported by ,Johnson, with the possible exception of Cepheus and NGO 2244, cannot be reproduced by a suitable mixture of graphite grain sizes. The curves for Cepheus and NGO 2244 have been plotted from observations of 5 and 3 stars respectively. Data for more stars arc required before we can accept the curves reported for these two regions. The most distinctive feature of graphite absorption, however, occurs in the ultra-violet. Very small graphite particles are able to produce a sharp quenching effect in the ultra-violet near 2200 A (Fig. 2). For a grain of radius 0·015μ, Qext(2200)/Qext(5470) ~ 12·3; the extinction thereafter decreases until at 1500 A, Qext(l500)/ Qext(5470) = 2·41. The quenching effect decreases in absolute value for larger sizes, but the maximum at 2200 A and a minimum at 1500 A remains (Fig. 3). There is a strong possibility that this is in fact the effect observed by Boggess and Borgman2• On the basis of graphite absorption one would also expect a fairly sharp drop in the extinction curvo towards 1500 A, This is in fact the romarkable outcome of a preliminary investigation by Dr. J. Borgman 1°. Such a result, if confirmed, would give strong support to the graphite grain theory. On the basis of pure ice grains it does not seem possible to explain the ultra-violet measurements4 • Moreover, rocont attempts to isofa,te certain infra-red interstellar absorption bands to be expected on the basis of ice or dielectric absorption have produced negative results11• Although the accuracy of the rocket experiments might be questioned, the absence of these bands if further established would provide additional evidence against ice absorption.

THE INHERITANCE OF AUTOIMMUNE DISEASE IN MICE: A STUDY OF HYBRIDS OF THE STRAINS NZB AND C3H.

As soon as our stock of NZB mice had been established (Holmes and Burnet, 1963 a), we initiated a programme of hybridisation in the hope of gaining information about the nature of the genetic difference responsible for autoimmune manifestations. The first cross established was with our C3H strain. The offspring were large brown mice, much more vigorous, long-lived and healthy than NZB. Relatively few developed a positive Coombs test and at a much later age than was the case with NZB. Kidney lesions of the severe type characteristic of NZB were never seen, but thymus lesions occurred in a large proportion. These F1 mice were studied extensively from serological and histological angles as were another relatively large group of mice obtained by backcrossing F1 with NZB. The findings from these studies, plus relevant information in regard to our 0311 strain, comprise the main part of this paper. One of our chief incentives to have a substantial supply of F1 mice was to study the influence of splenic and thymus grafts from the compatible NZB strain, on the appearance of autoimmune manifestations in a relatively insusceptible strain. The results of such experiments will be reported elsewhere. From the original point of view they were wholly negative but there was an interesting correlation of findings in host and grafted thymuses.