TY - JOUR
T1 - Impaired rearrangement of IgH V to DJ segments in bone marrow Pro-B cells from old mice
AU - Szabo, Paul
AU - Shen, Steven
AU - Telford, William
AU - Weksler, Marc E.
N1 - Funding Information:
The authors thank Dr. M. Schlissel for help in establishing the signal end “footprinting” assay in their laboratory as well many useful discussions, Drs. D. Smith and F. Jin for their help with flow cytometry and Michel Nussenzweig for the GFP mice. They also wish to acknowledge the contribution of the late Dr. E. Spanopoulou who encouraged them to undertake these studies. This work was supported in part by NIH Grant AG14669 and by the Harriman Foundation.
PY - 2003/3
Y1 - 2003/3
N2 - There are fewer bone marrow Pre-B cells in old compared to young mice. We have demonstrated both decreased rearrangement of the V to DJ IgH gene segments and low levels of VH germline transcripts in Pro-B cells, the precursors of Pre-B cells, from old compared to young mice. However, there was no difference in the level of RAG-mRNA in purified Pro-B cells from old and young mice. Consistent with the prior reports that fewer bone marrow emigrants enter the peripheral B cell populations of old than young mice, we identified fewer transitional B cells in the blood, as well as the spleen, of old than young mice. Association of impaired IgH rearrangement with a decreased number of transitional B cells in old mice was supported by finding that the percentage and number of transitional B cells expressing rearranged IgH and IgL transgenes, which do not require rearrangement of their endogenous IgH gene segments, were comparable in old and young mice. In contrast, the percentage and number of transitional B cells in these Ig-transgenic mice, which escaped allelic exclusion and have rearranged endogenous IgH gene segments, showed an age-associated decline similar to that seen in wild type mice. These data are consistent with the view that impaired V to DJ rearrangement contributes to the decreased levels of bone marrow Pre-B cells as well as the decreased levels of transitional B cells in the periphery.
AB - There are fewer bone marrow Pre-B cells in old compared to young mice. We have demonstrated both decreased rearrangement of the V to DJ IgH gene segments and low levels of VH germline transcripts in Pro-B cells, the precursors of Pre-B cells, from old compared to young mice. However, there was no difference in the level of RAG-mRNA in purified Pro-B cells from old and young mice. Consistent with the prior reports that fewer bone marrow emigrants enter the peripheral B cell populations of old than young mice, we identified fewer transitional B cells in the blood, as well as the spleen, of old than young mice. Association of impaired IgH rearrangement with a decreased number of transitional B cells in old mice was supported by finding that the percentage and number of transitional B cells expressing rearranged IgH and IgL transgenes, which do not require rearrangement of their endogenous IgH gene segments, were comparable in old and young mice. In contrast, the percentage and number of transitional B cells in these Ig-transgenic mice, which escaped allelic exclusion and have rearranged endogenous IgH gene segments, showed an age-associated decline similar to that seen in wild type mice. These data are consistent with the view that impaired V to DJ rearrangement contributes to the decreased levels of bone marrow Pre-B cells as well as the decreased levels of transitional B cells in the periphery.
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U2 - 10.1016/S0008-8749(03)00084-4
DO - 10.1016/S0008-8749(03)00084-4
M3 - Article
C2 - 12798310
AN - SCOPUS:0038206973
VL - 222
SP - 78
EP - 87
JO - Cellular Immunology
JF - Cellular Immunology
SN - 0008-8749
IS - 1
ER -