Lymphocyte subpopulations in the thymus of NZB x NZW mice: phenotypic characterization by flow cytofluorometry...

The composition of the thymocyte population was investigated as a function of age in the autoimmunity-prone NZB x NZW F1 (NZB x W) female mice and in control BALB/c female mice. Single- and two-colour flow cytofluorometry analyses were used to quantitate the cell surface binding of fluorochrome-conjugated antibodies directed against various lymphocyte markers and of fluoresceinated peanut agglutinin (PNA). In both mouse strains, two major phenotypically distinct thymocyte subpopulations were thus identified. The predominant subpopulation was characterized as bright Thy-1+, Lyt-1 + 2+ and bright PNA+, and the other one as dull Thy-1+, Lyt-1 + 2- and dull PNA+. The relative frequencies of these two subpopulations were similar in NZB x W and BALB/c mice at 3 months of age. However, from 6 months onwards, slight but significant differences became detectable between the two strains. Thus, in BALB/c mice, both thymocyte subpopulations regressed at approximately the same rate during ageing so that their relative proportions remained constant. In contrast, in NZB x W mice, while the number of bright Thy-1+ cells diminished as in BALB/c mice, the number of dull Thy-1+ cells barely varied from 3 to 12 months of age, which resulted in a proportional increase of this latter subpopulation. Moreover, elevated frequencies of surface immunoglobulin-bearing cells were recorded in the thymus of 8-12 month old NZB x W mice but not in BALB/c mice. Therefore, the development of autoimmunity in NZB x W mice appears associated with an abnormal age-dependent evolution of the intrathymic lymphocyte population.