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B-lineage cell deficits in bone marrow of lpr/lpr mice
1Unite d'Immunobiologie, CNRS URA 359, Institut Pasteur, Paris, France.
Abstract:
Analyses of bone marrow (BM) lymphocytes in C57BL/6 mice homozygous for the lpr mutation (B6.lpr) disclosed low numbers of pre-B and B cells, as compared with age-matched control B6 mice. BM depletion in B6.lpr mice was selective for B-lineage cells, appeared in young adults, and developed markedly with age and disease progression, contrasting with the peripheral lymphocyte hypercellularity. Normalization of pre-B and B cellularity in BM of B6.lpr mice was observed after administration of polyclonal Ig, that also markedly improved the clinical condition. Isolated pre-B (B220+ IgM-) cells from B6 or B6.lpr mice, however, showed essentially the same rates of IL-7-dependent proliferation and differentiation to B (IgM+) cells in culture, indicating that the BM B-lineage deficit is not the result of an intrinsic defect in B cell generation.
Insights
Bone marrow (BM) B-cell numbers are low in B6.lpr mice, contrasting with peripheral lymphocyte increases. Polyclonal immunoglobulin therapy normalized B-cell counts and improved clinical signs, suggesting a non-intrinsic B-cell generation defect.
Area of Science:
- Immunology
- Hematology
- Genetics
Background:
- C57BL/6 mice (B6) homozygous for the lpr mutation (B6.lpr) exhibit autoimmune disease.
- B6.lpr mice display peripheral lymphocyte hypercellularity but reduced bone marrow (BM) lymphocytes.
Purpose of the Study:
- To investigate the cause of B-cell deficiency in the BM of B6.lpr mice.
- To determine if the BM B-lineage deficit is due to an intrinsic defect in B-cell generation.
Main Methods:
- Comparative analysis of BM lymphocytes in B6.lpr and control B6 mice.
- Assessment of B-cell proliferation and differentiation in vitro.
- Evaluation of therapeutic effects of polyclonal immunoglobulin administration.
Main Results:
- B6.lpr mice showed significantly lower numbers of pre-B and B cells in the BM compared to B6 mice.
- The BM B-cell depletion was specific to B-lineage cells and worsened with age.
- Administration of polyclonal immunoglobulin normalized BM B-cell counts and improved clinical symptoms.
- Isolated pre-B cells from both B6 and B6.lpr mice exhibited similar IL-7-dependent proliferation and differentiation rates.
Conclusions:
- The bone marrow B-lineage deficit in B6.lpr mice is not caused by an intrinsic defect in B-cell generation.
- Polyclonal immunoglobulin therapy can restore B-cell cellularity and ameliorate disease in B6.lpr mice.
- The findings suggest an extrinsic factor contributing to B-cell deficiency in the BM of B6.lpr mice.