Similar rates of production of T and B lymphocytes in the bone marrow.
The rate of renewal of T lymphocytes in the bone marrow of euthymic C57BL/Ka and athymic nu/nu BALB/c mice was estimated by in vivo labeling with bromodeoxyuridine. T lymphocytes accounted for 16-18% of marrow cells in euthymic mice as judged by immunofluorescent staining with monoclonal antibodies for Thy-1, CD3, and alpha/beta T cell antigen receptor markers. About 70% of marrow cells expressed receptors (Mac-1, Gr-1, B220) for myeloid, macrophage, and B lineage cells. Approximately 13% of cells in the athymic bone marrow expressed alpha/beta T cell receptors. Sorted marrow T cells proliferated in response to stimulation with anti-alpha/beta antibodies in vitro and showed functional rearrangements of V beta and J beta genes. Sorted non-T cells did not respond to stimulation in vitro, and all V beta and J beta gene rearrangements identified were nonfunctional. In vivo labeling studies indicated that approximately 17 x 10(6) bone marrow T cells are renewed daily in euthymic mice and approximately 14 x 10(6) are renewed in athymic mice. Approximately 11 x 10(6) mature B cells (immunoglobulin M+) are renewed daily in the bone marrow of the latter mice. To determine whether marrow precursors can give rise to T cells directly, marrow cells from euthymic and athymic mice were depleted of T cells by cell sorting and incubated in vitro for 48 h in the absence of exogenous growth factors or thymic stromal cells. Examination of the cells after culture showed that 10-12% stained brightly for alpha/beta T cell receptors. Although functional rearrangements of V beta and J beta genes were not detected before culture, the majority of rearrangements were functional after culture. The emergence of the bright alpha/beta T cells in culture was dependent on depletion T cells from the marrow cells before culture. The results suggest that most marrow T cells are generated in the marrow itself.
Dejbakhsh-Jones
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S
Department of Medicine, Stanford University School of Medicine, California 94305, USA.
Okazaki
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H
Strober
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S
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D001402:B-Lymphocytes / Q000166:cytology*; D001483:Base Sequence; D001853:Bone Marrow / Q000276:immunology*; D017252:CD3 Complex / Q000032:analysis / Q000096:biosynthesis; D002454:Cell Differentiation; D006224:Cricetinae; D017931:DNA Primers; D005434:Flow Cytometry; D005803:Genes, Immunoglobulin; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology*; D007074:Immunoglobulin G; D007133:Immunoglobulin Joining Region / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis; D007438:Introns; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis / Q000096:biosynthesis; D013045:Species Specificity; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology*; D018800:Thy-1 Antigens / Q000032:analysis / Q000096:biosynthesis
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D017931:DNA Primers; D007074:Immunoglobulin G; D007133:Immunoglobulin Joining Region; D007135:Immunoglobulin Variable Region; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018800:Thy-1 Antigens