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B-cell-autonomous somatic mutation deficit following bone marrow transplant
A M Glas1, E H van Montfort, J Storek
1Virginia Mason Research Center and the Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Blood
|July 27, 2000
Summary
Bone marrow transplant recipients show impaired B cell function, specifically a reduced ability to accumulate somatic mutations. This defect in B cell mutation accumulation is intrinsic to the B cells themselves.
Area of Science:
- Immunology
- Hematology
- Transplantation
Background:
- Hematopoietic stem cell transplantation (HSCT) leads to prolonged humoral immunodeficiency.
- Previous studies ruled out V region repertoire issues as the cause of these deficiencies.
Purpose of the Study:
- To investigate the capacity of naive B cells from bone marrow transplant (BMT) recipients to accumulate somatic mutations.
- To determine if the observed defect in somatic mutation is B cell-autonomous or T cell-dependent.
Main Methods:
- Analysis of immunoglobulin gene rearrangements in BMT recipients and healthy subjects.
- Assessment of somatic hypermutation accumulation in naive B cells in a T-cell dependent manner.
- Co-culture experiments using BMT recipient and healthy subject B and T cells.
Main Results:
- BMT recipients exhibited significantly less somatic mutation in their immunoglobulin rearrangements compared to healthy subjects.
- Naive B cells from BMT recipients demonstrated a deficient capacity for T-cell-dependent somatic mutation accumulation.
- T cells from BMT recipients could not induce somatic mutation in autologous B cells but could in healthy B cells, indicating a B cell-autonomous defect.
Conclusions:
- Naive B cells from BMT recipients have an intrinsic deficit in accumulating somatic mutations.
- This B cell-autonomous defect contributes to the impaired humoral immune responses observed after HSCT.