TY - JOUR
T1 - Anti-μ treatment suppresses immunoglobulin light-chain gene expression and Peyer's patch development
AU - Woloschak, Gayle E.
AU - Krco, Christopher J.
AU - Rodriguez, Moses
N1 - Funding Information:
Acknow(edgemenrs-Thaeu thors wish to thank Kathy Jensen for typing this manuscript and Mary Jane Doerge, Beth Howie and Mabel Pierce for excellent technical assistance. This work was supported in part by American Cancer Society Grant IM-348, Fraternal Order of Eagles Grant No. 72 and the Mayo Foundation. Moses Rodriguez is the recipient of Teacher Investigator Award NS-00-849 from the National Institutes of Health.
PY - 1989/4
Y1 - 1989/4
N2 - 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.
AB - 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.
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U2 - 10.1016/0161-5890(89)90124-7
DO - 10.1016/0161-5890(89)90124-7
M3 - Article
C2 - 2497338
AN - SCOPUS:0024559685
SN - 0161-5890
VL - 26
SP - 351
EP - 358
JO - Molecular Immunology
JF - Molecular Immunology
IS - 4
ER -