Anti-μ treated mice have been used extensively as a model for suppressed B-cell development [Murgita R.A., Mattioli C.A. and Tomasi T.B., Jr. (1973) J. exp. Med.138, 209; Manning D.D. (1975) J. Reticuloendothel. Soc.18, 63; Manning D.D. and Jutila J.W. (1972) J. Immun.108, 282; Janeway C. A., Jr., Murgita R.A., Weinbaum F.I., Asofsky R. and Wigzell H. (1977) Proc. natn. Acad. Sci. U.S.A.74, 4582; Hayglass K.T., Naides S.J., Benacerraf B. and Sy M.-S. (1985) J. Molec. Cell. Immun.2, 107; Manning D.D. (1972) J. Immun.109, 1152; Cooper M.D., Kearney J.F., Gathings W.E. and Lawton A. R. (1980) Immun. Rev.52, 29; Burrows P.D., Kearney J.F., Lawton A.R. and Cooper M.D. (1978) J. Immun.120, 1526]. However, little molecular evaluation has been performed on these animals to determine the level at which B-lineage cells are arrested. Experiments reported here were designed to determine the effects of anti-μ treatment of newborn mice on Ig-specific mRNA expression in lymphocyte populations. Newborn CBA/J mice received i.p. injections of goat anti-μ IgG or non-immune goat IgG, every 2 days, from birth until age 4 weeks. The degree of B-cell suppression in anti-μ treated mice was evident by low serum Ig levels and lack of surface Ig+ cells in splenic lymphocytes. Morphologically, spleens of B-cell depleted mice were slightly reduced or normal size, while the total area of Peyer's patches (PP) was three-fold less than control mice. Spleen cells from anti-μ suppressed mice contained high levels of μ-mRNA, but markedly reduced levels of mRNA specific for other Ig heavy-chain isotypes, as determined by DNA excess dot blot and Northern blot hybridizations. RNA specific for other sequences (actin or IL-2 receptor) was not affected and hybridization to parent plasmid (pACYC) was not detected. In addition, suppression of κ- and λ-mRNA accumulation was evident. This was surprising, since the target for anti-μ treatment appears to be a B-cell population expressing intact surface IgM, a stage in B-cell development in which both μ- and light-chain-specific mRNA accumulation should be detected. Our results suggest one of the following models: (1) anti-μ treatment deletes all Ig+ cells from the animal, so that only μ expressing pre-B-cells remain; or (2) anti-μ suppresses B-cell development by inhibiting κ and λ transcription, perhaps by some feedback mechanism in which the presence of surface Ig is required to maintain light-chain transcription.
ASJC Scopus subject areas
- Molecular Biology